Mezinárodní konference Regenerativní medicína International Regenerative Medicine Conference. April 9 10, 2014, Brno Hotel Holiday Inn

Mezinárodní konference Regenerativní medicína 2014 2014 International Regenerative Medicine Conference

April 9 – 10, 2014, Brno Hotel Holiday Inn

Operační sály BLOCK ® Surgical Komplexní dodávka operačních sálů na klíč: konzultace, projekční činnost, vestavba s technologií a vybavením, servis. K výstavbě operačních a zákrokových sálů společnost BLOCK® vyvinula a neustále inovuje vlastní, moderní systém Surgical, připravený pro technologie budoucnosti.

Hlavní výhody: • Atraktivní horizontální členění • Barevná, materiálová a konstrukční proměnlivost • Jednoduchá odnímatelnost panelů • Dodatečná integrovatelnost technologií • BLOCK® je přímý výrobce systému Surgical • Vynikající poměr cena / výkon • Rychlost instalace • Antibakteriální povrchová úprava • Možnost desinfikovat parami H2O2 • Systém odpovídá vysokým nárokům na hygienickou nezávadnost, snadnou čistitelnost a desinfikovatelnost

Sídlo firmy: BLOCK a.s., Stulíková 1392, 198 00 Praha 9 Korespondenční adresa: BLOCK a.s., U kasáren 727, 757 01 Valašské Meziříčí Tel.: +420 571 670 111 Fax: +420 571 670 244 E-mail: [email protected]

w w w. bl o ck . c z

Národní Centrum Tkání a Buněk National Cell and Tissue Centre & 4MEDi – Centrum buněčné terapie a diagnostiky 4MEDi – Centre for Cell Therapy and Diagnostics

are organizing

2014 INTERNATIONAL REGENERATIVE MEDICINE CONFERENCE under the auspices of the Minister of Health of the Czech Republic

&

the Mayor of the statutory city of Brno

April 9 –10, 2014, Hotel Holiday Inn Brno, Czech Republic General Partner

Dear Colleagues It is with great pleasure to welcome you on behalf of the Organizing committee, the National Cell and Tissue Centre, the company 4MEDi and the collaborating partners to the 2014 International Regenerative Medicine Conference in Brno auspiced by the Czech Ministry of Healthcare and the Mayor of the statutory city of Brno. We are delighted to welcome all participating delegates to this excellent event. I trust that you are looking forward to hear two days of stimulating lectures and to have the opportunity of networking and to find new colleagues in the field of regenerative medicine. We have an excellent group of speakers covering the up-to-date hot topics, enthusiastic and keen to share their knowledge with you. We are very honored to be holding the Conference of rapidly developing field of medicine with a leading international representation for the first time in the Czech Republic. Thanks to a number of leading Czech medical institutions and important biotechnology companies, Czech Republic starts to be considered as a country where regenerative medicine is witnessing its explosive growth. The Conference will provide you with a very exciting programme of the up-to-date information and knowledge to enhance your own specialty areas of work. Take the opportunity to discuss with your colleagues, friends, partners and mentors. You will witness how long-term commitment and hard work has resulted in solid approaches with the acceptance in regenerative medicine. As you will see the international collaborations are expanding across the continents, as it is necessary to harmonize approaches, methods and regulation globally. Many thanks to the Organizing team of the Conference and the event supporting partners. We would not be able to run the Conference without their kind support and to bring inspired people together. I would like to thank each of you for attending our Conference and bringing your fruitful expertise to our gathering. The international collaboration within the field of regenerative medicine is very essential for successful development. You, as the main leading persons, have the vision, the knowledge and the experience to help us pave our way into the regenerative medicine future. I trust that you will return from the Conference inspired by excellent lectures and that you will have made new contacts that will support you in your essential work. I hope the Conference will fulfill your expectations and will allow you to actively contribute to the research and development in the field of tissue engineering and cell therapy in regenerative medicine. It is my pleasure to wish you all a successful Conference.

Václav Procházka Chair of the Conference

Vědecký výbor Konference Conference Scientific Committee MUDr. Václav Procházka, Ph.D. – předseda výboru / chair of the committee Fakultní nemocnice Ostrava University Hospital Ostrava

Prof. MUDr. Petr Arenberger, DrSc., MBA Fakultní nemocnice Královské Vinohrady University Hospital Royal Vineyards, Prague

Prof. MUDr. Roman Hájek, CSc. Fakultní nemocnice Ostrava University Hospital Ostrava

Prof. MUDr. Martin Krbec, CSc. Fakultní nemocnice Královské Vinohrady University Hospital Royal Vineyards, Prague

RNDr. Eva Matějková Národní Centrum Tkání a Buněk a.s. National Cell and Tissue Centre

Odborní partneři konference Conference Scientific Partners Fakultní nemocnice Brno University Hospital Brno

Fakultní nemocnice Ostrava University Hospital Ostrava

Fakultní nemocnice Královské Vinohrady University Hospital Royal Vineyards, Prague

Nemocnice Na Bulovce Hospital na Bulovce

3

Hlavní témata Konference

Conference Main Topics

1. Výzkum a vývoj Regenerativní medicíny 2. Současný vývoj v preklinických a klinických studiích 3. Současné světové trendy a výsledky oboru Regenerativní medicíny 4. Legislativní zázemí, regulace a etické otázky 5. Vývoj Regenerativní medicíny v České republice 6. Klinické využití Regenerativní medicíny 7. Buněčná terapie 8. Tkáňové inženýrství 9. Tkáňové transplantáty

1. Regenerative Medicine Research and Development 2. Current Development in Pre-Clinical and Clinical Studies 3. Current Global Trends and Results of Regenerative Medicine 4. Legislative environment, Regulations and Ethical Issues 5. Potential of Regenerative medicine in the Czech Republic 6. Clinical Use of Regenerative Medicine 7. Cell Therapy 8. Tissue Engineering 9. Tissue Transplants

Organizační výbor konference Organizing Committee Ing. Petr Koška, MBA Národní Centrum Tkání a Buněk National Cell and Tissue Centre RNDr. Eva Matějková Národní Centrum Tkání a Buněk National Cell and Tissue Centre MUDr. Dagmar Hrůzová PrimeCell Therapeutics a.s. Ing. Jakub Schůrek, MBA PrimeCell Therapeutics a.s. Andrea Gutová, M.A. PrimeCell Therapeutics a.s.

Vzdělávací akce je pořádána dle Stavovského předpisu ČLK č.16. Vzdělávací akce je pořádána podle vyhlášky MZČR č. 4/2010 Sb., kterou se stanoví kreditní systém pro vydání osvědčení k výkonu zdravotnického povolání bez přímého vedení nebo odborného dohledu zdravotnických pracovníků, ve znění vyhlášky č. 321/2008 Sb. Akce je akreditována u ČLK, KVVOPZ pro VŠ nelékaře a u ČAZL pro zdravotní laboranty a všeobecné sestry – účastníci obdrží certifikát o účasti.

Educational event organised according to Professional Prescription of the Czech Medical Chamber no. 16. Educational event organised according to Decree of the Ministry of Health of the Czech Republic no. 4/2010 Coll., which stipulates the credit system for the issue of certification for the performance of the healthcare profession without direct guidance or professional supervision of healthcare employees, as amended by Decree no. 321/2008 Coll.

4

Partneři konference Conference Partners Generální partner

Hlavní partner

Stříbrný partner

Bronzový partner

Mediální partneři Media partners

5

PROGRAM KONFERENCE / CONFERENCE PROGRAM

Program konference Conference Program Středa, 9. dubna Wednesday, April 9 8.00–09.15 9.30–9.45

Registrace účastníků Participants registration Slavnostní zahájení konference Welcome speech to the Conference

9. 45–11.45

Session I Development of Adult Adherent Stem Cell Therapeutics for CNS Injury and Disease Robert Deans Athersys, Inc., Cleveland, Ohio, USA Cell-Free Applications of Stem Cell Therapies Johnstone, Brian H. Indiana University-Purdue University Indianapolis, Indianapolis, USA Pluripotent Stem Cell-based Neural Disease Models Yuh-Man Sun Faculty of Medicine, the Department of Biology, Masaryk University, Brno, Czech Republic Cook Medical - Overview and Capabilities in Regenerative Medicine Jordi Marti COOK Medical Inc, Bloomington, IN, USA

11.45–12.00

Coffee break

12.00–14.00

Session II – Ortopedické indikace / Orthopedic indications Kultivované chondrocyty – naše zkušenosti, indikace a jejich limity Cultured Chondrocytes - Our Experience, Indications and Limits Martin Krbec, Filip Svatoš Ortopedicko-traumatologická klinika 3. LF UK a FNKV, Praha Department of Orthopaedics and Traumatology, University Hospital Royal Vineyards and The Third Faculty of Medicine, Charles University, Prague, Czech Republic Biological Resurfacing of Unicompartmental Knee and Ankle OA (Kissing Lesions) By MSCs Stefano Zanasi Villa Alba Hospital, Villa Maria Group, Bologna, Italy; University of Florence, Italy Řešení chondrálních defektů nosných kloubů metodou NTC chondrograft - hodnocení výsledků A method of solving chondral defects of weight-bearing joints by NTC chondrograft – evaluation of results Petr Vališ Ortopedická klinika Fakultní Nemocnice Brno Department of Orthopaedics, University Hospital Brno, Czech Republic Harvest BMAC Orthopedic Therapy Indications Dario Ponti Harvest Technologies Corporation, Plymouth, MA, USA Transplantace menisku Meniscus Transplantation Libor Paša Klinika traumatologie LF MU Brno, Úrazová Nemocnice Brno Department of Traumatology, Masaryk University, Faculty of Medicine, Brno, Trauma Hospital Brno

6

PROGRAM KONFERENCE / CONFERENCE PROGRAM

14.00–15.00

Oběd / Lunch

15.00–16.30

Session III Odběry krvetvorných buněk a dalších mononukleárních elementů z periferní krve; současné možnosti a moderní trendy. Collection of hematopoietic stem cells and other mononuclear cells from peripheral blood; current options and modern trends Zdeněk Kořístek Klinika hematoonkologie, Fakultní nemocnice Ostrava, Česká republika International Clinical Research Center, Fakultní nemocnice u Sv. Anny, Brno Department of Hematooncology, University Hospital Ostrava, Czech Republic International Clinical Research Center, St. Anne´s University Hospital Brno, Czech Republic Distribuce dovoz / vývoz krvetvorných buněk Distribution Import / Export of Hematopoietic Stem Cells Marie Kuříková Institut klinické a experimentální medicíny, Praha Institute for Clinical and Experimental Medicine, Prague, Czech Republic Naše zkušenosti s PRP při léčbě chronických defektů Our experience with the use of PRP in the treatment of chronic defects Petr Šíma Chirurgické oddělení, Fakultní nemocnice Plzeň Surgical Department, University Hospital Plzen, Czech Republic

16.30–16.45

Coffee break

16.45–18.00

Session IV – Ischemické indikace / Ischemic indications Stem Cell Therapy for NO-Critical Limb Ischemia and Diabetic Foot Václav Procházka Fakultní nemocnice Ostrava University Hospital Ostrava, Czech Republic Cell Therapy in NO-CLI Long-term Follow up Berthold Amann Asklepios Westklinikum Hamburg, Germany Cell Therapy in NO-CLI Comparison of Therapeutical Methods Juraj Maďarič Národný ústav srdcových a cievnych chorôb, a.s., Bratislava, Slovensko Autologous bone marrow stem cell : a possible solutions for end stage ischemic cardiomyopathy Eugenio Caradona Fondazione di Ricerca e Cura Giovanni Paolo II (Università Cattolica del Sacro Cuore)

18.00

Závěr prvního dne konference Conclusion of the first day of the conference Facility Tour of National Cell and Tissue Centre (Národní Centrum Tkání a Buněk) Gala Evening

18.00–19.00 20.00–00.00

7

PROGRAM KONFERENCE / CONFERENCE PROGRAM

Čtvrtek, 10. dubna Thursday, April 10 9.00–11.00

Session I Cord Blood Storage: New Horizons Keith L. March Indiana University-Purdue University Indianapolis, Indianapolis, USA Mutually exclusive or compatible: the future of allogeneic and autologous treatments Frida Grynspan Stem Cell Medicine, Israel Factors Influencing Yield and Composition of Regenerative Cell Preparations Eckhard Alt InGeneron, USA Current Hot Topics in Cell Therapy Keith L. March Indiana University-Purdue University Indianapolis, Indianapolis, USA

13.15–11.15

Coffee break

11.15–13.15

Session II Endothelial progenitor cells in angiogenesis for regenerative medicine Martin Klabusay International Clinical Research Center, St. Anne‘s University Hospital, Brno, CZ Regenerative medicine and cell technologies in Stem Cells Bank Pokrovsky, Russia Alexander Smolyaninov, Varvara Bagaeva Stem Cells Bank Pokrovsky, St. Petersburg, Russia Bioartificial Replacements of Blood Vessels - a Review Lucie Bačáková Fyziologický ústav AV ČR, v.v.i., Praha Institute of Physiology Academy of Science, Czech Republic, v.v.i.,Prague, Czech Republic Aortic Heart Valve Replacements Elena Filová Fyziologický ústav AV ČR, v.v.i., Praha Institute of Physiology Academy of Science, Czech Republic, v.v.i.,Prague, Czech Republic

13.15–14.15

Oběd/Lunch

14.15–15.45

Session III Clinimacs Prodigy in Regenerative Medicine Ivan Hutňan Miltenyi Biotec, Slovensko Regenerative Medicine: State of the Science John Fraser Cytori Therapeutics Inc., USA Legislativní rámec oboru Regenerativní medicína v ČR a EU The legislative framework for Regenerative medicine in the Czech Republic and the EU Eva Matějková Národní Centrum Tkání a Buněk, Brno National Cell and Tissue Centre, Brno KOMERČNÍ PREZENTACE: Generálního partnera BLOCK a.s. Commercial Presentation: General Partner BLOCK a.s.

15.45–16.00

Coffee break

8

PROGRAM KONFERENCE / CONFERENCE PROGRAM

16.00–17.00

Session IV – Tkáňové transplantáty/ Tissue Transplants Skin Banking: Current Products and Future Developments Cornelia D Richters Euro Tissue Bank, Beverwijk, The Netherlands Endothelial cell viability following PDAEK corneal grafting using an innovative microkeratome system Mor M. Dickman University Eye Clinic Maastricht Transplantace allogenního štěpu sterna k uzávěru post-sternotomických defektů hrudní stěny - výsledky 4 let úspěšné mezioborové spolupráce Transplantation of allogeneic sternal bone graft for closure of post sternotomy chest wall defects - results of four years of successful interdisciplinary collaboration Martin Kaláb Kardiochirurgická klinika Fakultní nemocnice Olomouc a Lékařská fakulta Univerzity Palackého Olomouc Department of Cardiac Surgery University Hospital and Faculty of Medicine Palacky University, Olomouc, Czech Republic Využití moderních technologií při přípravě produktů z lidských tkání pro léčebné použití u člověka. The use of modern technologies in processing of human tissue products for clinical use Ján Karkoška Národní Centrum Tkání a Buněk, Brno National Cell and Tissue Centre, Brno

17.00

Závěr konference / The end of Conference

9

10

REJSTŘÍK FIREM / COMPANIES DIRECTORY

Rejstřík firem Companies Directory BLOCK a.s. BLOCK a.s. od svého založení v roce 1991 poskytuje komplexní služby v projektové přípravě, výrobě a výstavbě investičních celků s náročnými technologiemi a vysokou kvalitou prostředí (čisté prostory), pro které rovněž zajišťuje následný servis a validace. Pro realizaci náročných staveb a technologií společnost vyvinula, vyrábí a dodává komplexní systémy, které jsou vytvářeny na základě dlouholetých zkušeností a prostorám tak zajišťují maximální spolehlivost. Tyto systémy zajišťuje v rámci sdružení firem BLOCK GROUP. Mezi hlavní oblasti působnosti BLOCK a.s. patří farmacie a biotechnologie, chemie, laboratoře, zdravotnictví, elektrotechnika a potravinářství. Aktivní činnost vyvíjí ve střední Evropě a Rusku. Kontaktní osoba: Ing. Zdeněk Kučera, email: [email protected], [email protected]

As of its foundation in 1991 BLOCK a.s. has been focused to complete services in the field of project preparation, production, construction, and follow-up service of capital investment sets with demanding technologies and high quality of environment (so called „clean rooms“) and validation. For the implementation of demanding constructions and technologies BLOCK has developed, produced, and delivered complete systems. These have been designed on the basis of long-term experience and provide premises with maximum reliability. BLOCK secures the production of all components for these systems within the BLOCK GROUP. Among the main corporate scopes of activity rank pharmacology and biotechnology, chemistry, laboratories, health service, as well as electrical and foodstuff industries. BLOCK is active in Central Europe and in Russia, Belarus and Ukraine. Contact person: Zdeněk Kučera, email: [email protected], [email protected]

BIOHEM spol. s r.o. BIOHEM was established in 1993 and today, after 12 years of existence, it profiled to a reputable distributor in Slovakia. The company supplies the Slovak pharmaceuticals and medical devices market. BIOHEM is a direct importer of wide range of pharmaceutical products, medical devices, laboratory diagnostics and medical instruments and has contracts with major multinational manufacturers such as BAXTER, Dade Behring, bioMerieux or Miltenyi Biotec.

EP Rožnov a.s. EP Rožnov a.s. je projekční, inženýrská a dodavatelská společnost, která poskytuje komplexní služby v investiční výstavbě, v oblasti náročných technologií. Specializací firmy je projektování a realizace čistých a klimatizovaných prostor v elektrotechnickém, automobilovém a farmaceutickém průmyslu, v optice a jemné mechanice, ve zdravotnictví, ve výrobě zdravotnické techniky i v oblasti výzkumu a vývoje. Váš partner pro čisté prostory Kontakt: [email protected]

EP Rožnov, a.s. is a design, engineering and supply company that provides services in the investment construction and in the area of demanding technologies. The company´s specialization is the design and implementation of clean rooms and air-conditioned spaces in the sphere of electrotechnical and automotive industry, pharmacy, optics and precision mechanics, health care, production of health care technology and research and development. Your partner for clean room Contact: [email protected]

11

REJSTŘÍK FIREM / COMPANIES DIRECTORY

HPST, s.r.o., Společnost HPST, s.r.o. je autorizovaným distributorem Agilent Technologies pro Českou republiku. Nabízí instrumentaci, autorizovaný servis a spotřební materiál pro atomovou a molekulární spektroskopii, plynovou a kapalinovou chromatografii, elektroforetické systémy, hmotnostní spektrometrii, disoluční zařízení, molekulární biologii a genomiku, automatické robotické systémy, nukleární magnetickou rezonanci a rentgenovou krystalografii. Kontaktní osoba: Daniela Tršová, manažer marketingu, e-mail: [email protected]

HPST, s.r.o. is an authorised Agilent Technologies distributor for the Czech Republic. It offers instrumentation, authorised service and consumables for atomic and molecular spectroscopy, gas and liquid chromatography, electrophoresis systems, mass spectrometry, dissolution equipment, molecular biology and genomics, automated robotic systems, nuclear magnetic resonance and X-ray crystallography. Contact person: Daniela Tršová, Marketing Manager, e-mail: [email protected].

Merci Společnost MERCI, s. r.o. je profesionálním partnerem v oblasti návrhů, realizace, vybavování a zásobování laboratoří a provozů laboratorním nábytkem, technologickými zařízeními a spotřebním materiálem. Naším zaměřením jsou především oblasti vědy, výzkumu, průmyslu, zdravotnictví a školství. Společnost MERCI, s. r.o. je členem České společnosti chemické, Asociace výrobců a dodavatelů zdravotnických prostředků a držitelem ocenění Česká kvalita a dalších certifikátů. Váš MERCI Team Kontaktní osoba: Pavel Spáčil, tel: 724 566 400, mail: [email protected]

MERCI, s.r.o., is a professional partner in the design, construction, equipping and supplying laboratories and facilities with laboratory furniture, technological equipment and consumables. We focus primarily on science, research, industry, healthcare and education. MERCI, s.r.o. is a member of the Ceska Spolecnost Chemicka (Czech Chemistry Society), Association of Manufacturers and Suppliers of Medical Devices and it is a holder of the Czech Quality Certification and other certificates. Your MERCI Team Contact person: Pavel Spacil e-mail: [email protected]

Morys s.r.o. Společnost MORYS s.r.o. již více než 20 let realizuje pro veřejné i soukromé investory a partnerské stavební společnosti komplexní dodávky novostaveb a rekonstrukcí, jako i specializované činnosti v oblasti technických zařízení budov - klimatizace, vzduchotechnika, vytápění, měření a regulace, zdravotechnika, elektroinstalace. Kontaktní osoba: Ing Radim Kviatkovský, e-mail: [email protected]

For over 20 years, the company MORYS s.r.o. has been implementing complex rendering of new buildings and reconstructions for public and private investors, as well as specialised activities in the field of technical equipment of buildings – air conditioning, air technology, heating, measurement and regulations, sanitary facilities, electrical installations. Contact person: Radim Kviatkovský, e-mail: [email protected]

12

REJSTŘÍK FIREM / COMPANIES DIRECTORY

Trigon PLUS s.r.o. Firma TRIGON PLUS je předním dodavatelem laboratorních přístrojů. Ke klíčovým nabízeným produktům patří technologie čistých prostor – laminární a ochranné boxy, kultivační zařízení s kontrolovaným prostředím – inkubátory s řízenou atmosférou, pracovní boxy – izolátory s filtrací a s řízenou atmosférou, zařízení na přípravu a skladování vzorků – centrifugy, lyofilizátory, chladící, mrazící zařízení, kryotechnologie, analytické přístroje. Prioritní činností firmy jsou komplexní služby – poradenství, prodej, školení, servis, validace a kalibrace. Certifikace ISO 9001, akreditovaná kalibrační laboratoř Zastoupení firmy THERMO Scientific – divize laboratorní techniky, RUSKINN, SYNGENE, LABOGENE a řady dalších. Kontakt: www.trigon-plus.cz, [email protected], tel. +420 272 680 190

The company TRIGON PLUS is one of the leading laboratory equipment suppliers. To the key offered products belongs clean rooms technologies – laminar and safety boxes, culture systems with controlled atmosphere – incubators with CO2/O2 control, workstations - isolators with filtration and CO2/O2 control, equipment for sample preparation and storage – centrifuges, freeze dryers, freezers, cold storage and cryopreservation equipment, analytical systems. The priority of the company is to offer complex services – consultancy, sale, training, service, validation and calibration. Certification ISO 9001, accredited Calibration Laboratory Representative of companies THERMO Scientific – Laboratory Equipment Division, RUSKINN, SYNGENE, LABOGENE and many others. Contact: www.trigon-plus.cz, [email protected], telephone +420 272 680 190

VIVACOM s.r.o. VIVACOM je moderní společností v oblasti péče o zdraví, zaměřenou na průzkum a marketing zdravotnických výrobků a zařízení. Hlavní vizí firmy je příspěvek společnosti prostřednictvím péče o zdraví, za pomoci unikátních technologií, které umožňují, aby lékařská péče byla vlídnější a příjemnější. Především si uvědomujeme, že spokojenost zákazníků je primárním elementem úspěchu ve vztahu s nimi a pracujeme společně, abychom vám poskytli mimořádné služby a co největší výběr kvalitních výrobků. Kontaktní osoba: Michal Vikus, Managing Director, e-mail: [email protected]

VIVACOM s.r.o. is a modern company providing services in the area of healthcare which focuses on research and marketing of healthcare products and equipment. The company’s key vision is to contribute to the society via healthcare using unique technologies which allow it to be more patient-friendly and comfortable. We are acutely aware that patient satisfaction is paramount for establishing a successful relationship with them and we work together to provide you with extraordinary services and the broadest selection of quality products possible. Contact person: Michal Vikus, Managing Director, e-mail: [email protected]

Frigomont a.s. Frigomont a.s. zajišťuje vybavení operačních sálů, laboratoří, farmaceutických provozů včetně stavební a výrobní technologie, projektů, inženýringu a stavebního dozoru.

Frigomont provides equipment for operating rooms, laboratories, and for pharmaceutical operations including construction and manufacturing technologies, design and engineering and construction supervision.

13

14

SBORNÍK ABSTRAKT ABSTRACT BOOK

15

OBSAH / CONTENT

Obsah Content Development of Adult Adherent Stem Cell Therapeutics for CNS Injury and Disease . . . . . . . . . . . . . . 20 Cell-Free Applications of Stem Cell Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Pluripotent Stem Cell-based Neural Disease Models. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Cook Medical - Overview and Capabilities in Regenerative Medicine . . . . . . . . . . . . . . . . . . . . . . . . 23 Kultivované chondrocyty – naše zkušenosti, indikace a jejich limity . . . . . . . . . . . . . . . . . . . . . . . . 24 Cultured Chondrocytes - Our Experience, Indications and Limits. . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Biological Resurfacing of Unicompartmental Knee and Ankle OA (Kissing Lesions) By MSCs. . . . . . . . . 25 Ošetření chondrálních defektů nosných kloubů metodou implantace solidního chondrograftu . . . . . . 27 Treatment of Chondral Defects of Weight-Bearing Joints by Implanting Solid Chondrograft. . . . . . . . . 27 Harvest BMAC Orthopedic Therapy Indications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Transplantace menisku . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Meniscus Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Distribuce dovoz / vývoz krvetvorných buněk. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Distribution Import / Export of Hematopoietic Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Naše zkušenosti s PRP při léčbě chronických defektů . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Our Experience with the Use of PRP in Treatment of Chronic Defects . . . . . . . . . . . . . . . . . . . . . . . . 33 Stem Cell Therapy for NO-Critical Limb Ischemia and Diabetic Foot . . . . . . . . . . . . . . . . . . . . . . . . . 35 Cell Therapy in No-option Critical Limb Ischemia – Comparison of Therapeutic Methods and Predictors of Therapeutic Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Cell therapy in No-option CLI: state of the art and long-term results . . . . . . . . . . . . . . . . . . . . . . . . 38 Autologous bone marrow stem cell: a possible solutions for end stage ischemic cardiomyopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 The enhancement of T cell-mediated immune responses through the use of beta lactams. . . . . . . . . . . 42 Factors Influencing Yield and Composition of Regenerative Cell Preparations . . . . . . . . . . . . . . . . . . 43 Regenerative Medicine and Cell Technologies in Stem Cells Bank Pokrovsky, Russia . . . . . . . . . . . . . . 44 Bioartificial Replacements of Blood Vessels – a Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Aortic Heart Valve Replacements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Clinimacs Prodigy in Regenerative Medicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

16

OBSAH / CONTENT

Legislativní rámec oboru Regenerativní medicína v ČR a EU. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 The Legislative Framework for Regenerative Medicine in the Czech Republic and the EU . . . . . . . . . . . 48 Transplantace allogenního štěpu sterna k uzávěru post-sternotomických defektů hrudní stěny – výsledky 4 let úspěšné mezioborové spolupráce . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Transplantation of allogeneic sternal bone graft for closure of post sternotomy chest wall defects – results of four years of successful interdisciplinary collaboration . . . . . . . . . . . . . . . . . . . . 49 Skin Banking - Current Products and Future Developments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 The use of modern technologies in processing of human tissue products for clinical use . . . . . . . . . . . 51

17

SEZNAM PŘEDNÁŠEJÍCÍCH / THE LIST OF SPEAKERS

Seznam přednášejících The list of speakers Eckhard Alt InGeneron, USA Berthold Amann Asklepios Westklinikum Hamburg, Germany Varvara Bagaeva Stem Cells Bank Pokrovsky, St. Peterburg, Russia Lucie Bačáková Fyziologický ústav AV ČR, v.v.i. / Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i. Brian H. Johnstone Indiana University-Purdue University Indianapolis, Indianapolis, USA Eugenio Caradona Fondazione di Ricerca e Cura Giovanni Paolo II (Università Cattolica del Sacro Cuore), Italy Robert Deans Athersys, Cleveland, Ohio, USA Mor M. Dickman University Eye Clinic Maastricht, The Netherlands Elena Filová Fyziologický ústav AV ČR, v.v.i. / Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i. John Fraser Cytori Therapeutics Inc., USA Frida Grynspan Stem Cell Medicine, Israel Ivan Hutňan Miltenyi Biotec, Slovakia Martin Kaláb Fakultní nemocnice Olomouc / University Hospital Olomouc, Czech Republic Ján Karkoška Národní Centrum Tkání a Buněk, Brno / National Cell and Tissue Centre, Brno, Czech Republic Martin Klabusay International Clinical Research Center, St. Anne‘s University Hospital, Brno, Czech Republic Zdeněk Kořístek Klinika hematoonkologie, Fakultní nemocnice Ostrava / Department of Hematooncology, University Hospital Ostrava, Czech Republic / International Clinical Research Center, St. Anne´s University Hospital Brno, Czech Republic

18

SEZNAM PŘEDNÁŠEJÍCÍCH / THE LIST OF SPEAKERS

Martin Krbec Fakultní nemocnice Královské Vinohrady, Praha / University Hospital Royal Vineyards, Prague, Czech Republic Marie Kuříková Český registr dárců krvetvorných buněk, Institut klinické a experimentální medicíny, Praha Czech Stem Cells Registry, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Juraj Maďarič Národný ústav srdcových a cievnych chorôb, a.s., Bratislava, Slovensko / The National Institute of Cardiovascular Diseases, Bratislava, Slovakia Keith L. March Indiana University-Purdue University Indianapolis, Indianapolis, In, USA Jordi Marti COOK Medical Inc, Bloomington, IN, USA Eva Matějková Národní Centrum Tkání a Buněk, Brno / National Cell and Tissue Centre, Brno, Czech Republic Libor Paša Úrazová nemocnice Brno / Trauma Hospital Brno, Czech Republic Václav Procházka Fakultní nemocnice Ostrava, / University Hospital Ostrava Cornelia D Richters Euro Tissue Bank, Beverwijk, The Netherlands Dario Ponti Harvest Technologies Corporation, Plymouth, MA, USA Alexander Smolyaninov Stem Cells Bank Pokrovsky, St. Peterburg, Russia Yuh-Man Sun Biologický ústav Lékařské fakulty, Masarykova univerzita Brno, Česká republika / Faculty of Medicine, the Department of Biology, Masaryk University, Brno Filip Svatoš Fakultní nemocnice Královské Vinohrady, Praha University Hospital Royal Vineyards Petr Šíma Fakultní nemocnice Plzeň / University Hospital Pilzen, Czech Republic Petr Vališ Fakultní nemocnice Brno / University Hospital Brno, Czech Republic Stefano Zanasi Villa Alba Hospital, Bologna (Italy) / Clinical Professor University of Florence, Italy

19

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Development of Adult Adherent Stem Cell Therapeutics for CNS Injury and Disease Robert Deans Athersys, Inc., Cleveland, Ohio, USA

Adult stem cell therapeutics have entered an exciting development phase, with late phase clinical studies supporting approval studies in disease settings of significant unmet need. Athersys has created a clinical manufacturing platform for an adherent bone marrow derived cell product, MultiStem®, and is in Phase II development for treatment of stroke with a pipeline of activity in TBI, spinal cord and multiple sclerosis. Emphasis has been placed on understanding mechanistic action and biodistribution of infused cells, with increased understanding that modulation of the systemic immune system is central at driving repair of acute CNS injury. Data will be presented from preclinical models of CNS disease with relevance to optimizing clinical design and progressing to commercialization.

20

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Cell-Free Applications of Stem Cell Therapies Brian H. Johnstone, Yansheng Du and Keith L. March Indiana University School of Medicine, Indianapolis, Indiana, USA

Adipose-derived stem cells (ASC) are a plentiful source of multipotent cells obtained by minimally invasive extraction methods from subcutaneous adipose tissues. ASC share many phenotypic and physiological attributes with bone marrow-derived mesenchymal stem cells (BM-MSC). It is becoming increasingly evident that the predominant mode of action of both cell types is paracrine support of endogenous tissues. We have been investigating the therapeutic potential of a cell-free product consisting of paracrine factors produced during culture of ASC. This ASC-conditioned medium (ASC-CM) protects and repairs neurons of the central and peripheral nervous systems; importantly, even when administered following the initial insult. Employing a neonatal model of hypoxia-ischemia (HI) injury (or birth asphyxia), robust preservation of brain volume and function was maintained with intravenous administration of ASC-CM up to 36 hours after inducing injury. Similarly, administration of ASC-CM to mice transgenic for a mutation in the superoxide dismutase-1 (SOD-1) gene associated with familial amytrophic lateral sclerosis (ALS), significantly extended the lifespan of these mice. Neutralization of either insulin-like growth factor-1 (IGF-1) or brain-derived neurotrophic factor (BDNF) reduced but did not abolish the neuroprotective activity of ASC-CM in the HI injury model. Thus, the neuroprotective activity of ASC-CM is produced by a combination of potent neurotrophic and survival factors functioning together and individually to affect protection and repair of damaged tissues. Current efforts are directed at developing a good manufacturing process for ASC-CM production that follows current international regulatory standards for cell and tissue products. The goal is to develop off-theshelf ASC-CM drug for the treatment of severe neurological diseases.

21

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Pluripotent Stem Cell-based Neural Disease Models Yuh-Man Sun Faculty of Medicine, the Department of Biology, Masaryk University, 625 00 Brno, Czech Republic

The advent of technological developments in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is changing the landscape of biomedical research by shifting model organism-based disease systems to pluripotent stem cell-based disease systems. Conventional research often interprets biological phenomena in humans using the wealth of knowledge that is extrapolated from model organism-based studies, which may cause erroneous translations due to the species’ differences derived from evolutionary gaps. Pluripotent stem cell-based disease models offer desirable patient–based (or personalised) disease systems without breaking the ethical constraints and also circumvent the difficulties in obtaining samples. We are interested in adopting the cutting-edge iPSC technology, which enables the generation of neurons and glias straight from patients’ skin biopsies. The iPSC technology transforms the skin samples of individual patients into a personalized cellular-basis neural cultural system, by which the personal neural cells that are engraved with the characteristic signatures from original donors will provide a tool for uncovering the cause of aberrant functions in patient brains. The iPSC and ESC technology provides a powerful tool for investigating gene functions in patients’ samples and supplies endless samples for research.

22

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Cook Medical - Overview and Capabilities in Regenerative Medicine Jordi Marti COOK Medical Inc, Bloomington, IN, USA

For the last 50 years, Cook Medical has worked with researchers and physicians across 42 medical specialties to develop simpler, more effective therapeutic tools. Today these tools support emerging cell therapies and regenerative medicine technologies, helping to advance these promising treatments from the lab to the patient. Cook laboratory products such as human platelet lysate and cryogenic storage vials enable the efficient and safe production of cell therapies, while newly developed devices – a cardiac catheter, an infusion needle, and a pressure transducer – bring control to the delivery of cells to the patient. Finally, a Cook extracellular matrix material (SIS) continues to provide a regenerative therapy option for patients suffering from a variety of medical conditions.

23

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Kultivované chondrocyty – naše zkušenosti, indikace a jejich limity Svatoš F., Bartoška R., Čech P., Klézl Z., Džupa V., Krbec M. Fakultní nemocnice Královské Vinohrady, Praha

Autoři hodnotí vlastní soubor 48 pacientů s implantovanými kultivovanými chondrocyty. Podávají přehled indikací, dělí pacienty a výsledky dle lokalit vhodných k implantaci. Dále seznamují s vlastním průběhem odběru, kultivace i implantace chondrograftu. Podávají přehled o vývoji Lysholmova skóre v průběhu léčby. Poukazují na limity implantací. Ukazují vlastní pohled na indikace a kontraindikace a zhodnocení komplikací a jejich řešení. V neposlední řadě pak seznamují s úskalími vlastní metody i procesu odběru a zpracování graftu a seznamují s legislativními překážkami. Na několika krátkých kazuistikách ukazují úspěchy, ale i neúspěchy u vlastních pacientů souboru a dávají ke zvážení změny celého procesu, včetně indikačních kritérií.

Cultured Chondrocytes - Our Experience, Indications and Limits Svatoš F., Bartoška R., Čech P., Klézl Z., Džupa V., Krbec M. University Hospital Royal Vineyards, Prague, Czech republic

The authors evaluated their own sample group of 48 patients with implanted cultivated chondrocytes. They present an overview of the indications, and divide the patients and results according to localities suitable for implantation. They also provide an outline of the actual course of the taking, cultivation and implantation of the chondrograft. They present an overview of the development of the Lysholm score during the course of treatment, and draw attention to the limits of implantations. The authors additionally present their own view of the indications and contraindications, as well as an assessment of the complications and the solutions thereto. Last but not least they familiarise us with the range of their own methods in the process of taking and processing the graft, and present an outline of the legislative obstacles. In a number of brief case studies they show the successes and also the failures in the patients within the sample group and present potential changes to the entire process, including indication criteria, for our consideration.

24

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Biological Resurfacing of Unicompartmental Knee and Ankle OA (Kissing Lesions) By MSCs Stefano Zanasi, Gaetano Maci, Gaetano Carriere, Monica Pastina Corresponding Author: Stefano Zanasi Villa Alba Hospital, Villa Maria Group, Bologna, Italy

Introduction Lesions involving articular cartilage of the knee and talus are extremely common in clinical practice and affect scores of individuals worldwide. Their origin is frequently traumatic in nature, although degenerative cartilage pathologies also compose a large proportion of cases. Early therapy is important as untreated lesions have the tendency to become chronic, increasing in both size and severity so that requiring implant arthroplasty. In fact, cartilage tissue has a low intrinsic capacity for regeneration and as such does not heal spontaneously, therefore, the damage may be irreversible and lead to chronic symptoms and early osteoarthritis, with a share ranging from 17% to 50% of cases. Various surgical options have been proposed to repair knee and talar dome cartilage defect, but among them, only osteochondral grafting and autologous chondrocyte implantation have shown the ability to provide reconstruction of the lesion site with hyaline cartilage. Nevertheless, the need for two operations and high costs remain drawbacks of autologous chondrocyte implantation. Mesenchymal stem cells (MSCs) are proposed as a new option for treatment of articular cartilage defects because of their ability to differentiate into various lineages, including osteoblasts and chondrocytes. MSC differentiation in the specific track may be achieved as a result of environment, mechanical stimulation, and growth factors present in the platelet gel, able to stimulate cells toward osteogenesis and chondrogenesis. The potential of a multipotent cell may be considered not only an intrinsic capability of the cell alone but also the interaction between a cell with its physiologic niche that provides a signaling network (ie, the extracellular matrix, adhesion molecules, growth factors, cytokines, and chemokines secreted by the resident cells). Autologous bone marrow contains not only stem cells and precursor cells as a source of regeneration tissue, but also accessory cells that support angiogenesis and vasculogenesis by producing several growth factors. This suggests no cell selection and expansion in the laboratory may be required (as with autologous chondrocyte implantation), and consequently the transplant can be performed in one operative procedure. In patients younger than 50 years, affected by unicompartmental osteoarthritis of the knee or ankle, to avoid or delay implant arthroplasty, we have obtained very promising results by biological coating of both kissed joint cartilage defects resorting to MSCs. Materials and Methods From 6/2008 to 12/2011 we implanted MSCs by arthroscopic or mini-open technique in 31 patients (16m/15f ) affected by unicompartmental osteoarthritis Ahlback stage II/III for medial (5) and lateral (2) unicompartmental femuro-tibial OA, patella-femoral joint OA (18), and 6 unshouldered kissed ankle large defects. The average age was 32yrs. (19-55). All patients were followed for a minimum follow-up of 24months (12-42ms). We excluded patients younger than 15 years or older than 55 years. Malalignment of the lower limb and the presence of joint laxity were considered relative contraindications to be corrected if present. The ethical committee of our institution approved the human protocol for this investigation and written informed consent was signed by all the patients enrolled in this study. The mean size of the lesions was 9.5cm2 (range 5.5 – 27 cm2), and the mean depth of the lesions was 4.2 ± 1.4 mm. We recorded the ICRS as well as AOFAS score preoperatively. A standard radiographic examination, including AP and lateral weightbearing views and MRI of the affected joints were performed preoperatively. The scaffold used in this series for cell support was a hyaluronic acid membrane (HYAFF®-11; Fidia Advanced Biopolymers) with addition of platelet gel. The secretory granules of platelets, the α granules, contain platelet-derived growth factors AA, BB, and AB; transforming growth factors β1 (TGF-β1) and β2; platelet-derived epidermal growth factor; platelet-derived angiogenesis factor; insulin growth factor 1; and platelet factor 4, which influences bone regeneration. Because of commercial availability, the first 23 patients were treated using as a scaffold the hyaluronic acid membrane, whereas the last 8 patients received in addition to the graft an human amniotic membrane patch covering by the stromal face. The technique consists of taking, using a disposable kit, 60 ml of bone marrow aspiration from the ipsilateral anterior iliac crest in a sterile regimen, with the patient in a supine decubitus position and under general or spinal anesthesia, and centrifuging (Harvest PreP2 Smart System i.e.) 5-6 times to concentrate contained mesenchymal cells in the bone marrow. Through the use of thrombin from autologous blood collection,

25

SBORNÍK ABSTRAKT / ABSTRACT BOOK

you can turn the bone marrow and produce a concentrated gel : Hyaluronic acid membrane is cut in an appropriate size following the area of the lesion and loaded by capillarity with 2 mL bone marrow concentrate and 1 mL platelet-rich fibrin gel (Harvest SmartPReP®2 APC+™System) to reconstruct both side of the kissed chondral defect with miniopen or arthroscopic procedure. In the last 8 cases Human Amniotic Membrane by Tissues Bank was positioned with the stromal side over the graft surface and fixed with fibrin glue (Tissucol, Baxter). Patients are then directed to a specific rehabilitation program. Results We followed patients at 3, 6, 12, 18, and 24 months after surgery. The clinical evaluation was performed using the ICRS-IKDC and AOFAS protocol; the evaluation of the cartilage was performed by a 1.5T MRI imaging and processing was performed by MOCART scoring system. The EuroQol EQ-5D was used to assess the quality of life of patients. The ICRS-IKDC and AOFAS scoring documented a statistically significant improvement in clinical objective and subjective data (p0.0001). We had no intraoperative as well as postop complications. The mean preoperative ICRSIKDC as well as AOFAS score were respectively 56.4 ± 16.5 and 51±11.2. The mean ICRS-IKDC as well as AOFAS score improved to 81.3 ± 6.7 at 6 months follow-up, 88.2 ± 7.6 at 12 months, 89.9 ± 4.5 at 18 months, and 90.4 ± 3.7 at 24 months. The EuroQol EQ-5D index was significantly improved compared to baseline in all patients. NMR imaging at 3,6,12 and 24 ms f.up revealed a complete filling of the defect in 91%, a complete integration of the border area with the adjacent cartilage in 94% with intact and homogeneous tissue repair and intact subchondral lamina and subchondral bone in 89% and 78% of cases respectively, with total average MOCART score of 87out of 100. It has not been demonstrated at clinical as well X-Ray film f.up progression of preoperative OA. The 12 ms to 24ms second-look surgery 6 cases showed good coverage (> 90%) and the integration of the grafts. Histology at 12 ms. f.up documented hyaline fibrous tissue with a high content of collagen type II and proteoglycans, that is the maturation in progress of implanted MSCs to a clear fibro-hyaline-like phenotype without peculiar cell organization. Discussion and Conclusions These results suggest that MSCs resurfacing procedure even in severe unicompartmental osteoarthritis demonstrates as an effective treatment for a biological coating that provides at least at medium-term data, remission of pain and swelling, with good functional recovery and the ability to resume previous work activity and finally it demonstrates overlapping outcome vs ACT procedure with the advantage of a single operative step, without requiring removal of a cartilage sample for cloning in a specialized center and replanting after about 40 days, with consequent and important cost reductions.

26

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Ošetření chondrálních defektů nosných kloubů metodou implantace solidního chondrograftu Vališ P., Otaševič T., Rouchal M., Novák J., Repko M., Krbec M., Šprláková A´ Ortopedická klinika Fakultní Nemocnice Brno

Úvod Léčba chondrálních a osteochondrální defektů nosných kloubů (kolene, hlezna) představují stále vážný terapeutický problém, především pro minimální schopnost reparace hyalinní kloubní chrupavky. K hlavním příčinám poškození kloubní chrupavky řadíme traumata, opakované mikrotraumatizace a avaskulární nekroźy. Všechny defekty kloubního povrchu je nutné považovat za preartrotický stav. Nejspolehlivější zobrazovací metodou, která určí rozsah poškození chrupavky i pod ní ležící kosti zůstává magnetická resonance. Přímé posouzení stavu kloubního povrchu a poměrů v kloubu a současné ošetření defektu umožňuje artroskopie. V současné době je popsáno velké množství postupů k ošetření chondrálních defektů. Materiál a metoda Metodu implantace solidního chondrograftu s využitím autologních chondrocytů pro ošetření defektů nosných kloubů používáme na naší klinice od roku 2001. Za tu dobu bylo odoperováno celkem 132 pacientů. U 79 byl defekt lokalizován na kondylech femuru, ve 21 případech na patele a 31 v oblasti hlezenního kloubu, u 1 pacientky se jednalo o náhradu chrupavky v loketním kloubu. Průměrný věk pacientů v době implantace činí 29 let. Interval pooperační sledování 5–156 měsíců, průměrná doba sledování 46 měsíců. Při výrobě solidního chondrograftu jsme spolupracovali s Tkáňovou bankou FN Brno, v současné době výrobu zajišťuje Národní tkáňové centrum Brno. Při operacích na kolenním kloubu jsme připojili ve 20 případech plastiku LCA a 1 x plastiku LCA a LCP a ve 13 případech plastiku závěsného aparátu pately. Při kontrolních ASK jsme odebírali vzorky z místa původní implantace chopndrograftu a histologicky je hodnotili Výsledky Pooperační sledování zahrnuje pravidelné klinické vyšetření a vyplnění Lysholmovy bodovací stupnice. S odstupem jednoho, dvou a pěti let od operace pacientům bylo provedena kontrolní MRI vyšetření. Závěr Dle našich zkušeností právě tato metoda poskytuje nejlepší klinické výsledky a zajišťuje obnovu hyalinní kloubní chrupavky.

Treatment of Chondral Defects of Weight-Bearing Joints by Implanting Solid Chondrograft Vališ P., Otaševič T., Rouchal M., Novák J., Repko M., Krbec M., Šprláková A´ Department of Orthopedics, University Hospital Brno, Czech Republic

Introduction Treatment of chondral and osteochondral defects of weight-bearing joints (knee, ankle) still represents a serious therapeutic problem, primarily for the minimal ability to repair the articular hyaline cartilage. Main causes of damage to articular cartilage include trauma, repetitive microtraumatisation and avascular necrosis. All the defects of the articular surface must be considered to be a pre-arthritis condition. Magnetic resonance remains to be the most reliable imaging method which determines the extent of damage to the cartilage and the bone located under it. Arthroscopy allows for direct assessment of the articular surface and the conditions in the joint and for treatment of the defect. A number of procedures are currently described for the treatment of chondral defects.

27

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Material and Method The method of implanting a solid chondrografts using autologous chondrocytes to treat defects in weight-bearing joints has been used at our clinic since 2001. Over this period of time, surgery has been provided to a total of 132 patients. In 79 of them a defect was localised on femoral condyle, in 21 cases on the patella and in 31 in the ankle area. In 1 patient a replacement of cartilage in the elbow joint was provided. The average age of patients at the time of implantation is 29. The postoperative follow-up interval ranges from 5 to 156 months, the average follow-up time is 46 months. The solid chondrograft was manufactured together with Tissue Bank at the University Hospital in Brno. Currently, it is manufactured by National Cell and Tissue Centre, Brno. Of knee joint operations, we carried out ACL reconstruction in 20 cases and once both ACL and PCL reconstructions and in 13 cases a reconstruction of the attachment apparatus of patella. In the follow-up arthroscopies, samples were taken from the location of the original implantation of chondrograft and were subjected to histological examination. Results The post-operative monitoring includes regular clinical examination and filling out the Lysholm scoring scale. After one, two and five years from the surgery, patients were given a follow-up MRI examination. Conclusion Based upon our experience, this method provides the best clinical results and ensures restoration of hyaline articular cartilage.

28

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Harvest BMAC Orthopedic Therapy Indications Dario Ponti Harvest Technologies Corporation, Cellular Therapy & Education, Plymouth, MA, USA

Harvest Technologies has decades of cumulative experience designing, manufacturing and marketing devices for physiological biologic component separation, platelet sequestration, bone marrow derived stem cell harvesting and adipose graft consolidation. Our mission is focused on the development of unique, risk based approach techniques employing user friendly technologies empowering physicians to treat a wide variety of serious vascular, orthopedic and cardiovascular diseases based on evidence based research thereby improving surgical outcomes by accelerating the body’s own natural healing process. The Harvest SmartPReP System technology is a point of care multi-biologic platform to produce various Autologous Regenerative Cell (ARC) concentrates ranging from peripheral blood to produce Autologous Platelet Concentrate (APC+®), bone marrow aspirate to produce Bone Marrow Aspirate Concentrate [BMAC®] and liposuction adipose tissue to produce AdiPReP® Graft Matrix.

29

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Transplantace menisku Libor Paša Klinika traumatologie Lékař. Fakulty MU Brno, Úrazová nemocnice Brno

Úvod: Autoři prezentují své zkušenosti s transplantací hluboce mražených menisků. Metoda: Po odstranění poraněné části menisku se zvyšuje zátěž na měrnou jednotku chrupavky kolenního kloubu 3-4x oproti zdravému. Tyto změny vedou k časnému opotřebení chrupavek a následné poúrazové artróze. Transplantace menisku umožní zmírnit zátěžové síly na chrupavku a tím oddálit její opotřebení. Vhojení tkáně hluboce mraženého alogenního menisku Materiál: Autoři provedli celkem 71 transplantací menisku u 69 pacientů v období 2002-2013. Prvních 17 pacientů bylo odoperováno pomocí artrotomie, další pacienti již pomocí artroskopické techniky. Fixace obou rohů menisků byla vždy přes kostní kanálky k tibiálnímu platu, baze menisků byla fixována ke kloubnímu pouzdru pomocí stehů. V případě současné nestability byla provedena i rekonstrukce zkřížených vazů, v případě osové anulace do varozity byla provedena valgizační osteotomie proximální tibie, u 11 pacientů ve 2 dobách, u 12 pacientů současně s transplantací. Výsledky: Ve všech případech došlo ke vhojení transplantátu menisku. Ve 3 případech byla provedena artroskopie do 4 měsíců od transplantace, 1x pro bolesti nálezem 2 cm nepřihojené části menisku, která byla okrvavena a ošetřena 3 stehy, 2x pro výrazný nástup artrofibrotických změn, které byly při artroskopii odstraněny. K poranění transplantátu došlo u 2 pacientů, v období 25 a 29 měsíců od operace, u obou byla provedena menisektomie poraněné části menisku. Hodnota IKDC byla před transplantací v průměru 59, zatímco po 2 letech byla v průměru 81, Lysholm skore bylo v průměru 62 před operací a 91 po 2 letech. Diskuse: Transplantace menisku zlepšila životní komfort v 70 případech pozitivně, pouze u 1 pacienta byly udávány potíže výraznější, než před operací (artrofibroza). Zhodnocení rtg a subjektivního skore po 5 letech vykazovalo stacionární hodnoty a nedocházelo k progresi klinických potíží a artrotických změn i přesto, že 68% pacientů začalo klouby zatěžovat více, než před transplantací z důvodů snížení klinických potíží. Závěr: Transplantace alogenní tkáně menisku je metoda, která přináší zlepšení pohybového komfortu pacienta a dle našeho sledování přispívá ke zmírnění až zastavení progrese artrotických změn po předchozí menisektomii.

Meniscus Transplantation Libor Paša Traumatology Clinic of the Medical Faculty of Masaryk University in Brno, Trauma Hospital Brno

Introduction: The authors present their experiences with the transplantation of deep-frozen menisci.

30

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Method: After removing the injured part of the meniscus, the burden on the unit of measure of the knee joint cartilage is increased by 3-4x as against a healthy one. These changes lead to premature deterioration of the knee joint and subsequently to post-accident arthrosis. Transplantation of the meniscus enables alleviation of burden forces on the knee joint, thus delaying its deterioration. The recovery of tissue of a deep-frozen allogeneic meniscus Material: The authors carried out a total of 71 meniscal transplants in 69 patients during 2002-2013. The first 17 patients were operated with the aid of arthrotomy, the remaining patients with the aid of arthroscopic technology. The fixation of both menisci corners was always via the ostial valves to the tibial plateau, the base of the menisci was fixed to the joint capsule with the aid of stitches. Reconstruction of the crossed ligaments was carried out in cases of current instability, valgisation osteotomy of the proximal tibia was carried out in cases of axial annulment, in two periods in 11 patients, simultaneously with the operation in 12 patients. Results: Recovery of the meniscal graft occurred in all cases. In 3 cases, an arthroscopy was carried out within 4 months of the transplant: 1x due to pain located in a 2 cm part of the meniscus which had not healed, the blood of which was drained and treated with 3 stitches; 2x due to marked commencement of arthrofibrotic changes, which were removed by arthroscopy. Injury of the graft occurred in 2 patients, during a period of 25 and 29 months after the operation. A meniscectomy of the injured part of the meniscus was carried out in both. The IKDC value was at an average of 59 prior to the operation, whereas after 2 years it was at an average of 81; the Lysholm score was at an average of 62 prior to the operation and 91 after two years. Discussion: Transplantation of the meniscus improved life comfort positively in 70 cases; only in one patient were ostensive difficulties more marked than prior to the operation (arthrofibrosis). The radiographic evaluation and subjective score after 5 years demonstrated stationary values, and progression of clinical difficulties and arthritic changes did not occur even despite the fact that the joints started to burden 68% of patients more than prior to the transplantation due to a reduction of clinical difficulties. Conclusion: Transplantation of the allogeneic meniscal tissue is a method which brings improvement to a patient’s comfort of movement, and according to our monitoring it contributes to the alleviation to cessation of the progression of arthritic changes after a preceding meniscectomy.

31

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Distribuce dovoz / vývoz krvetvorných buněk Marie Kuříková Český registr dárců krvetvorných buněk Institut klinické a experimentální medicíny, Praha

Institut klinické a experimentální medicíny, Praha V přednášce bude prezentován přehled mezinárodní spolupráce Českého registru dárců krvetvorných buněk (CSCR), která je nezbytná pro zajištění tohoto typu transplantací. Dalším tématem bude srovnání legislativních požadavků na zajištění transportu v jednotlivých ze¬mích. Registr také funguje v souladu s mezinárodními akreditačními požadavky, které budou prezentovány s důrazem na transplantace hematopoetických kmenových buněk. Dále bude představena problematika přípravy transportu krvetvorných buněk pro vývoz i dovoz. Samostatnou kapitolou pak bude přehled možných nežádoucích událostí při transportu.

Distribution Import / Export of Hematopoietic Stem Cells Marie Kuříková Czech Stem Cells Registry Institute for Clinical and Experimental Medicine, Prague, Czech Republic

The lecture will present an overview of international collaboration of the Czech Stem Cells Registry (CSCR) necessary to provide for this type of transplantation. Another theme consists of a comparison of legislative requirements for transport conditions in individual countries. The Register also operates in keeping with international accreditation requirements which shall be presented with an emphasis on hematopoietic stem cell transplantation. Further, the issue of preparation necessary for hematopoietic stem cells transport designated both for export and import will be presented. An independent topic will consist of an overview of potential adverse events during transport.

32

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Naše zkušenosti s PRP při léčbě chronických defektů P. Šíma, M. Blažek, V. Karnos, V. Šanda Chirurgické oddělení Fakultní nemocnice Plzeň, primář: MUDr. V. Karnos

Projekt č. TA02011402 byl řešen s finanční podporou TA ČR program ALFA. Úvod Postupně narůstající počet diabetických a ischemických ran dolních končetin vede k novým přístupům léčby těchto defektů. Práce představuje prvotní zkušenosti s léčbou ran pomocí obohacené krevní plasmy na chirurgickém oddělení. Materiál a metodika Pacienti byli randomizováni do léčebné a kontrolní skupiny. Do studie jsme zařadili 40 pacientů s chronickým defektem, 25 pacientů bylo léčeno obohacenou krevní plasmou. Kontrolní skupinu tvořilo 15 nemocných léčených konvenční terapií. Planimetricky bylo hodnoceno zmenšování plochy a hloubky defektu v obou skupinách. Nemocní byli kontrolováni 0., 14., 28. den a dále v měsíčních intervalech, výsledky obou skupin byly porovnány a statisticky vyhodnoceny. Výsledky V léčebné skupině došlo u 8 nemocných ke kompletnímu zhojení defektu během 6ti měsíců, u ostatních došlo k signifikantnímu snížení velikosti defektu. V léčebné skupině došlo ke zmenšení plochy defektu o 2,4 cm2 /+-2,4cm2 / a snížení hloubky defektu o 2,1mm/+-2,5/, v porovnání s kontrolní skupinou, kde změna plochy defektu byla – 1,3cm2 /+-2,1cm2/ a změna hloubky – 1,0 mm /+-2,9mm/ Závěr Prokázali jsme, že použití obohacené plasmy při léčbě chronických defektů má pozitivní význam na granulační i epitelizační fázi hojení. Jedná se o novou metodu léčby, kde je zapotřebí přesně stanovit indikační kritéria použití. Klíčová slova diabetická noha - obohacená plasma – vlhké krytí

Our Experience with the Use of PRP in Treatment of Chronic Defects P. Šíma, M. Blažek, V. Karnos, V. Šanda Department of Surgery, University Hospital Pilsen, Czech Republic, Chief physician: MUDr. V. Karnos

Introduction The gradually increasing number of diabetes and ischemic wounds of the lower limbs leads to new approaches to treatment of these defects. The paper presents our initial experience with treatment of wounds using enriched blood plasma at the surgery department. Material and methodology Patients were randomised into a treatment group and a control group. The study included 40 patients with a chronic defect; 25 patients were treated with enriched blood plasma. The control group consisted of 15 patients treated with conventional therapy. Planimetry was used to evaluate the reduction of the area and defect depth in both groups. Patients were checked on day 0, 14 and 28 and, subsequently, in monthly intervals. The results from both groups were compared and statistically evaluated.

33

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Results In the treatment group, a total healing occurred in 8 patients during 6 months; in the other patients, there was a significant decrease in the defect size. In the treatment group the surface decreased by 2.4 cm2 /+-2.4cm2 / and the defect depth reduced by 2.1mm/+-2.5/ compared to the control group in which the change in the defect surface amounted to – 1.3cm2 /+-2.1cm2/ and the change of depth reached – 1.0 mm /+-2.9mm/ Conclusion We demonstrated that the use of enriched blood plasma in the treatment of chronic defects has a positive impact on both the granulation and epithelisation phase of healing. This is new treatment method in which the indication criteria for use must be precisely designated. Key words diabetic foot - enriched plasma - wet wound dressing

34

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Stem Cell Therapy for NO-Critical Limb Ischemia and Diabetic Foot Václav Procházka University Hospital Ostrava: Czech Republic

Toto téma bylo řešeno a jeho výsledky vznikly v rámci projektu SulgeliX TA02011313, který byl řešen s finanční podporou TA ČR program ALFA. History v NO-CLI stem cell therapy: In 1997 Asahara identified a class of bone-marrow derived progenitor cells that contribute to angiogenesis in ischemic tissue. The first clinical trial of autologous cell therapy in patients with CLI was published in 2002 by Tateishi-Yuyama, et al., who reported that patients treated with mononuclear cells isolated from bone marrow demonstrated improved hemodynamic measurements. Since this promising start, researchers have accumulated a decade of experience in the use of autologous cell therapy for NO-CLI with clinical trials progressing from retrospective case series to prospective studies and finally to several recent randomized controlled trials (RCTs). Randomized controlled trials of autologous cell therapy in NO-CLI Author

Year

N Total

N Treated

N Control

Source

Concentration Etiology technique

Follow up (mo)

Benoit

2011

48

34

14

BM

POC

ASO

6

Lu

2011

82

41

41

BM

Ficoll

ASO

6

Powell

2011

46

32

14

BM-Ex

Cell culture

ASO

6

Walter

2011

40

19

21

BM

Ficoll

ASO/TAO

3

Prochazka

2010

96

42

54

BM

POC

ASO

4

Arai

2006

25

13

12

BM

Cell separator

ASO

1

Huang

2005

28

14

14

PB

Cell separator

ASO

3

Totals: 365 195 170 BM = bone marrow; BM-Ex = bone marrow cells ex vivo culture expanded; PB = peripheral blood; ASO = atherosclerosis; TAO = thromboangiitis obliterans; NR = not recorded; POC = point of care centrifugation

Methodology of stem cells processing: Most autologous cell therapy protocols use bone marrow mononuclear cells (BMMNCs). Cell separators are automated machines, operated by a specialized technician or hematologist, which can isolate mononuclear cells from bone marrow aspirate (BMA). The Harvest SmartPReP device is a point of care, automated centrifuge system which processes the bone marrow aspirate with minimal manipulation, never removing the cells from their native plasma environment. Operation of the device does not require specialized personnel or transport of samples outside of the procedure room, which minimizes error and allows the entire process to be performed under the total supervision of the treating physician. The processing time is roughly 15 minutes, which allows bone marrow harvesting, processing, and delivery of autologous cell therapy to be completed during a single trip to the procedure room. Furthermore, the Harvest SmartPReP device prepares autologous cell concentrate from 240 mL of bone marrow aspirate, a volume which may be harvested without need for general anesthesia and is low enough to limit hemodynamic adverse events. NO-CLI stem cell application study: The aim of our study was to prevent major limb amputation (MLA) in this group of patients using a local application of autologous bone marrow stem cells concentrate. A total of 96 patients with CLI and foot ulcer (FU) were randomized into Group I and II. Patients in Group I, n=42 (36 males, 6 females, 66.2 ± 10.6 years) underwent local treatment with ABMSC while those in Group II, n=54 (control, 42 males, 12 females, 64.1 ± 8.6 years) received standard medical care. The frequency of major limb amputation in Group I and II was 21% and 44% within the 120 days

35

SBORNÍK ABSTRAKT / ABSTRACT BOOK

of follow up, respectively (p<0.05). Only in salvaged limbs of Group I both Toe pressure and Toe brachial index increased (from 22.66 ± 5.32 to 25.63 ± 4.75 mmHg and from 0.14 ± 0.03 to 0.17 ± 0.03, respectively, Mean ± SEM). This difference was statistically significant (p<0.040). We conclude ABMSC therapy results in 79% limb salvage in patients suffering from CLI and FU. In the remaining 21% lymphopenia and thrombocytopenia were identified as potential causative factors suggesting that at least a partial correction with platelet supplementation may be beneficial. Most important point The CD34+ cell counts in bone marrow concentrate (BMC) decreased (correlation, p=0.024) with age, even though there was no correlation between age and healing. An unexpected finding was made of relative, bone marrow lymphopenia in the initial bone marrow concentrates in patients who failed ABMSC therapy (21% of MLA). Most promising thing recently discovered Stromal vascular fraction from fat tissue lipoaspirate play important role in preventing MLA (Major limb amputation) in 75% of patients even with renal insuficiency and poor bonne marrow aspirate. It may be additional tool for NO-CLI patients treatment. Most concerning thing recently discovered SVF-ASC may have additional role in metabolic, imunomodulation and imunosupressive effect in patients with T2DM and critical limb ischemia for wound healing, glyc HbAlc and and other metabolic markers. Some interesting point Mesenchymal stem cells may be described as pericytic cells and have a consequences similar to “drug store” with multipotent effects in different diseases.

36

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Cell Therapy in No-option Critical Limb Ischemia – Comparison of Therapeutic Methods and Predictors of Therapeutic Effect Madaric J1,2, Klepanec A1,2, Altaner C3, Valachovicova M1, Mistrik M4, Necpal R2, Vulev I1,2. 1 Slovak Medical University, 2National Institute of Cardiovascular Disease, 3Institute of Experimental Oncology, Slovak Academy of Science, 4Clinic of Hematology and Transfusiology, Faculty Hospital, Bratislava, Slovakia

Background The aim of our study was to assess the effects of intramuscular (IM) and intraarterial (IA) bone marrow cells (BMCs) application in patients (pts) with “no-option“ critical limb ischemia (CLI), and to address factors associated with the therapeutic benefit of cellular therapy. Methods Seventy pts (age 64±11 years, M:F 61:9) with advanced CLI (Rutherford category 5,6) not eligible for revascularization were randomized to treatment with 40ml of bone marrow mononuclear cells (SmartPreP2 System) either using local intramuscular (n=36) or selective intra-arterial infusion (n=34). The primary end-point was limb salvage at 12-months follow-up. In subgroup of 41 pts, biological properties of mesenchymal stem cells (MSCs) were characterized according to their expression of cell surface markers and secretion of 27 cytokines, chemokines and growth factors. Pts with limb salvage and wound healing were considered as responders to BMCs therapy. Results The limb salvage was present in 77% (48/62 pts) at 12-months, eight pts died unrelated to stem cells therapy at 1-year follow-up (11%). In responders, a significant improvement in tcpO2, pain scale, quality of life, and Rutherford category was noted at 6 months persisting up to 12-months. There were no differences in IM versus IA application after 6 as well as 12-months in all observed parameters. In the subgroup analysis of 41 pts, responders (27 pts) were characterized by higher bone-marrow CD34+ cell counts (CD34+ 29±15×10^6 vs 17±12×10^6, p<0.05) despite a similar number of total nucleated cells (4.3±1.4×10^9 vs 4.1±1.2×10^9, p=0.66), by lower C-reactive protein levels (18±28 vs 100±96 mg/L, p<0.05) as well as serum leukocytes (8.3±2.1×10^9/L vs 12.3±4.5×10^9/L, p<0.05) as compared with non-responders (14 pts). By multivariate analysis the number of administrated CD34+ cells >20x10^6 emerged as an independent predictor of clinical benefit (p=0.03). In addition, expression of cell markers CD44 and CD90 in MSCs of responders was significantly higher as compared with non-responders (p<0.02). Secretome of responders revealed also significantly higher secretion levels of IL-4 (p<0.05), IL-6 (p<0.01), and MIP-1b (p<0.03) compared with non-responders. Conclusion Both IM and IA cells delivery are effective and comparable methods of therapy of patients with NO-CLI. A higher concentration of CD34+ cells, in parallel with higher concentration of MSCs is associated with better clinical outcome. Synergic effect of endothelial progenitors and MSCs, mediated by the paracrine effects appears to play crucial role in complex mechanism of cell therapy.

37

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Cell therapy in No-option CLI: state of the art and long-term results Berthold Amann Asklepios Westklinikum Hamburg, Germany

Critical limb ischemia (CLI) is the most advanced stage of PAD and has a high mortality and amputation rate. Wherever possible, the attempt to improve the revascularization of the leg arterial blood should be carried out. However, revascularization either with a surgical bypass or an endovascular procedure is primarily not or not any more possible in 20-30 % of CLI patients. These patients are called no-option CLI patients (NO-CLI) and have a grim prognosis, mostly ending with leg amputation. In Germany, about 25.000 major amputations are performed yearly due to CLI, about 100.000 in the US: In the last 15 years, the concept of a natural bypass has been developed. In short, basic science has shown that the growth of collateral arteries which can replace the transport function of a native occluded artery, is an active process directed by pericollateral monocytic cells which immigrate from the bone marrow. In the setting of ischemia, bone marrow cells are recruited, travel along a cytokine gradient to the ischemic area/the occluded artery and transmigrate into the pericollateral space. Her, they secrete cytokines, proteases and hormones which induce collateral artery growth which optimally restores blood flow in the ischemic area. This physiologic repair process however does not work in i.e. people with diabetes or advanced atherosclerosis. Here, the bone marrow response to ischemia is blunted (“diabetic mobilopathy”, Di Persio 2011), and collateral growth is not sufficient. The goal of cell therapy is to bring bone marrow cells into the ischemic region in order to induce collateral artery growth. From 1994 onwards, animal studies with autologous bone marrow cells (BMC)or cultured/expanded subfractions of bone marrow cells demonstrated the basic ability of locally implanted cells to stimulate collateral artery growth in a clinically meaningful way resulting in less necrosis or gangrene and increased exercise capacity. The first randomized clinical trial ( TACT – Study, Lancet 2002) on safety and efficacy of autologous bone marrow cell therapy in patients with peripheral arterial occlusive disease showed in addition to the practicality and safe application of the method the improvement of hemodynamic parameters, better wound healing and pain reduction. Following this publication, in a number of case or case control series , an increase of hemodynamic surrogate parameters ( ABI, TBI , oxygen tension ) were confirmed, as well as a reduction of pain , along with an improved quality of life. Since 2012, several meta-analyses have been published, all favoring cell therapy over placebo. The safety record is impeccable- with more than 1200 patients published, there was a zero-procedure related mortality and less than 5% minor morbidity. Limb salvage rates are between 45 and 65% depending on the collective studied. The application of cell therapy in diabetic foot/peripheral artery disease will be demonstrated, with case reports and case series as well as results from a randomized multicentric study in Germany. Furthermore, own long term results up to 6 years and the long term results from literature will be discussed.

38

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Autologous bone marrow stem cell: a possible solutions for end stage ischemic cardiomyopathy Eugenio Caradonna, Carlo Maria De Filippo Fondazione di Ricerca e Cura Giovanni Paolo II (Università Cattolica del Sacro Cuore)

Implantation of bone marrow stem cell (BMSC) in the myocardium is feasible and safe. Clinical outcome have been controversial 1. Isolated BMSC, mainly CD34+ CD133+, have been utilized in almost all the studies. The process to repair the ischemic myocardium is complex and involves cardiac stem cells, BMSC, cytokines and platelets2. Autologous bone marrow aspirate concentrate (BMAC), obtained by using a point of care device, has been infused intracoronary in patients with positive results 3. BMAC consists of a heterogeneous cell population, including hematopoietic, mesenchymal, progenitor cells as well as granulocytes and platelets. BMAC has the full complement of the nucleated cellular niche suspended in its natural plasma environment. These components are involved in the repair of the ischemic event. We report 11 patients with ischemic congestive heart failure and BMAC implantation. Five patients untreatable coronary artery disease (CAD) underwent BMAC implantation directly into the myocardium via left anterior thoracotomy. Six patients with ischemic cardiomyopathy, received BMAC in the area of viable myocardium and no graftable vessels during the operation of coronary artery by pass (CABG). Methods Eleven patients with ischemic cardiomyopathy, underwent autologous fresh BMAC implantation Six pts received BMAC during operation for cabg in the zone with viable myocardium and absence of suitable coronary artery (Group I). Five pts. were treated with BMAC via left anterior thoracotomy (Group II). Age of the pts ranged between 56 and 75 yrs. EF% was between 15-57%. All patients were considered inoperable due to poor quality of the coronary arteries by our internal validation system as well as by independent Institutions . The Catholic University Ethical Committee approved the treatment. Informed Consent was obtained by all participants. Dobutamine echocardiography and MRI were utilized to evaluate the presence of viable myocardium. Two patients with ICD underwent single photo emission tomography (SPET). The segments involved were anterior, antero-lateral and postero lateral. Surgical Technique Under general anesthesia, 120 ml of BM , aspirated from the posterior iliac crest, were processed to produce 20 ml of BMAC using a point- of-care system (Harvest BMAC System; Harvest Technologies GmbH, Munich, Germany) according to the manufacturer’s instructions. One ml of BM and 1 ml of BMAC were sent to the laboratory for cytometric analysis (Beckman Coulter Navios). During the 15 minute processing period, the patient was repositioned to a prone position. Group I: during routine cabg, before to remove the aortic occlusion, 20 ml of BMAC were injected in the target area. Group II: through a small anterior thoracotomy, BMAC was implanted into the myocardium via 20 injections of 1 ml each (22 gauge needle). The segments involved were the anterior and lateral wall of the left ventricle. Perioperative care Cardiac index was measured on an hourly base. Continuous electrocardiographic monitoring with automatic arrhythmia detection was maintained for 7 days post surgery. Echocardiography was performed inter-operatively and at one week. Follow-up visit was conducted at 1, 6 and 12 months. All patients underwent 24-hour Holter recording, echocardiography and MRI (2 pt. SPET). Results BM aspirate and BMAC of goup II are expressed in the following panel Table 1. Of notie we observed an increase in the circulating stem cells the day after the operation. For Group I the data are similar.

39

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Table 1 Platelets and stem cells concentration :Fist line Bone marrow , second line BMAC , third line preoperative peripheral blood , fourth line post operative peripheral blood. Group II. Platelets

CD34

CD34

CD133

CD133

CD117

CD117

(c-kit)

(c-kit)

CD309

CD309

%

cell x106 % ml

cell x 106 % ml

cell x 106 % ml

PLT 99

1,778%

0,25

0,148%

0,021

0,958%

0,140

0,014%

NC

PLT 401

1,970%

1,31

0,156%

0,104

1,286%

0,850

0,019%

NC

PLT 262

0,190%

0,012

0,042%

0,002

0,152%

0,009

0,015%

NC

PLT 252

0,140%

0,011

0,037%

0,002

0,136%

0,009

0,008%

NC

PLT 109

0,664%

0,05

0,096%

0,008

0,380%

0,030

0,010%

NC

PLT 641

0,879%

0,36

0,043%

0,018

0,500%

0,200

0,027%

NC

PLT 272

0,120%

0,006

0,013%

0,001

0,280%

0,015

0,020%

NC

PLT 248

0,330%

0,019

0,068%

0,004

0,119%

0,007

0,011%

NC

PLT 118

1,02%

0,170

0,23%

0,038

0,15%

0,025

0,021%

NC

PLT 390

1,19%

0,650

0,30%

0,160

0,18%

0,099

0,029%

NC

PLT 292

0,129%

0,005

0,023%

0,001

0,250%

0,015

0,020%

NC

PLT 267

0,326%

0,015

0,056%

0,003

0,126%

0,007

0,011%

NC

PLT 121

2,05%

0,690

0,12%

0,080

2,68%

0,810

0,04%

NC

PLT 43

2,30%

0,990

0,13%

0,110

2,61%

1,400

0,010%

NC

PLT 252

0,130%

0,009

0,016%

0,001

0,280%

0,015

0,020%

NC

PLT 266

0,200%

0,015

0,048%

0,004

0,119%

0,007

0,011%

NC

PLT 112

1,130%

0,220

0,130%

0,020

1,050%

0,200

0,007%

NC

PLT 487

1,02%

0,850

0,10%

0,080

0,92%

0,770

0,01%

NC

PLT 158

0,107%

0,006

0,063%

0,004

0,021%

0,001

0,008%

NC

PLT 142

0,293%

0,014

0,355%

0,018

0,015%

0,001

0,129%

NC

Group II Immediately after the injections, the cardiac index spontaneously increased. All the patients were discharged on the 7th post operative day. Arrhythmias were not recorded. At six months follow-up 4 patients were in class NYHA I and 1 in class II, EF increased (mean increase 6%) Echocardiography and MRI showed positive remodeling of the left ventricle (fig. 2). Late enhancement reduction (LE) (25% vs 50%) was present in the medial e basal segments of two pts. where BMAC was injected. Three have completed 1 yy. follow-up and are in NYHA I. Group I All patients had an uneventful postoperative course. At a mean follow up of two year they are in NYHA class I. Positive remodeling of the left ventricle was observed in all patients.

Discussion BMSCs have been used in ischemic heart failure with limited positive results1. A single population of cells was delivered in almost all the studies. BMAC contains the majority of the components for the repair of the ischemic damage. The importance of the cooperation between different cell populations has been addressed by Williams et. al. 4. Cytokines are triggered by the ischemic events and play a major role in the interactions between cells in the process to restore the damaged myocardium and in the evolution of hibernation toward apoptosis.

40

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Platelets produce several factors as VEGF, SDF-1, that are important for homing, differentiation of endothelial progenitor cell toward endothelial cell and mobilization of cardiac stem cells for myocardial repair 5. Patients with ischemic cardiomyopathy and not operable CAD treated with BMAC (Group II), have had a substantial improvement in EF, NYHA class, left ventricle positive remodeling and in the quality of life). Stem cells were increased in the early post operative period, suggesting a positive effect on the bone marrow-cardiac axis. Patients with cabg and BMAC (Group II) haven’t had complications and are in NYHA class I. This results prove that BMAC implantation is safe. Further studies are needed to confirm the positive improvement obtained in the remodeling of the heart and in the quality of life of the patients Bibliography 1. Jeevanantham V, Butler M, Saad A, Abdel-Latif A, Zuba-Surma EK, Dawn B. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis. Circulation. 2012 Jul 31;126(5):551–68. 2. Maltais S, Perrault LP, Ly HQ. The bone marrow–cardiac axis: role of endothelial progenitor cells in heart failure. European Journal of Cardio-Thoracic Surgery. 2011 Mar;39(3):368–74. 3. Turan RG, Bozdag-Turan I, Ortak J, Akin I, Kische S, Schneider H, et al. Improved Mobilization of the CD34 +and CD133 +Bone Marrow-Derived Circulating Progenitor Cells by Freshly Isolated Intracoronary Bone Marrow Cell Transplantation in Patients with Ischemic Heart Disease. Stem Cells and Development. 2011 Sep;20(9):1491–501. 4. Williams ARA, Hatzistergos KEK, Addicott BB, McCall FF, Carvalho DD, Suncion VV, et al. Enhanced Effect of Combining Human Cardiac Stem Cells and Bone Marrow Mesenchymal Stem Cells to Reduce Infarct Size and to Restore Cardiac Function After Myocardial Infarction. Circulation . 2013 Jan 14;127(2):213–23. 5. Tang J-M, Wang J-N, Zhang L, Zheng F, Yang J-Y, Kong X, et al. VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart. Cardiovasc. Res. 91:402–11.

41

SBORNÍK ABSTRAKT / ABSTRACT BOOK

The enhancement of T cell-mediated immune responses through the use of beta lactams. Frida Grynspan Stem Cell Medicine Ltd, Jerusalem, Israel

Remarkable advances have been made in understanding the mechanisms of action of T cells in cancer and autoimmune disease. Stem Cell Medicine Ltd believes that the clinical outcomes of cellular therapies can be improved through the combination with traditional pharmaceutical products. One such approach is the use of beta-lactams in the preparation of T-cell populations used in the treatment of tumors. Results have shown that beta lactams inhibit tumor growth in a T cell lymphoma mice model (RMA). In addition beta lactams are able to inhibit CD4+ differentiation to Th-2 through the inhibition of STAT6 and 18 Nf-κB related genes (Mor F & Cohen IR 2013). Further, beta lactams were shown to down-regulate 11 TGF-β related genes. TGF-β is known to induce CD4+ T cell differentiation to Treg (Wan YY 2008). Both Th2 cells and Treg are inhibitors of the Th1 response. These results indicate that beta lactams act through the suppression of a number of genes to affect CD4+ cell differentiation and provide a clear evidence of the potential of these compounds to act as anti-cancer agents by enhancing Th1 immunity and suppressing CD4+ cell differentiation to Th2 and Treg.

42

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Factors Influencing Yield and Composition of Regenerative Cell Preparations Eckhard Alt, Michael Coleman InGeneron, Inc, Houston, TX, USA, InGeneron, GmbH, Munich, Germany

Cell therapies utilizing autologous regenerative cells prepared at point-of care and administered within the same procedure are used with increasing frequency in a wide range of indications including aesthetic and reconstructive surgery, heart and vascular disease, osteoarthritis, orthopedics, and non-healing wounds. Unlike cell therapies comprised of cultured cells and produced in large batches as biopharmaceuticals these personalized cell preparations may vary based on patient and methodological factors. Patient factors such as age, lifestyle, disease status, and concomitant medications are known to influence characteristics of the cell preparation, but these factors may not be easily altered. However, methodological factors under control of the clinician including tissue source and anatomical location, and technologies utilized for tissue acquisition and cell isolation may have dramatic effects on the final cell preparation. Aronowitz and coworkers (Plastic and Reconstructive Surgery, 2013, 132(6):932-939) recently compared four in-clinic systems for isolation of adipose derived cells and found significant differences between the systems in cell yield, residual collagenase activity, and in the proportion of colony forming fibroblasts. This presentation will summarize results reported in the scientific literature as well as our own results for preparation of adipose tissue and umbilical cord matrix derived regenerative cells.

43

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Regenerative Medicine and Cell Technologies in Stem Cells Bank Pokrovsky, Russia V Bagaeva, A Aiezenshtadt, A Smolyaninov Stem cells bank Pokrovsky, Sankt-Petersburg, Russia

Regenerative medicine is the „process of replacing or regenerating human cells, tissues or organs to restore or establish normal function“. In our laboratory we consider on two directions: 1. Mesenchymal stem cells as regenerative technology basis 2. Fibroblasts for patients with burn and for cosmetology Mesenchymal stem cells (MSC) are pluripotent stem cells with fibroblasts like morphology, high proliferative potential and definite immunophenotype: CD34-, CD44+, CD45-, CD90+, CD105+ etc. It can be characterized by capacity to adhesion to culture plastic, differentiation potential to adipose, chondrogenic and osteogenic lines. MSC possess a wild spectrum of biology active action: immunomodulatory, stimulation of angiogenesis, antiapoptotic and antinecrotic effects etc. So MSC became a most popular sourсe for regenerative and cellular therapy. There are more than three hundred and half clinical trials based on MSC application in international clinical trials database. Including application of allogenic MSC. Safety of MSC application isn’t question anymore. In our laboratory we create bank of certified MSC cultures from different source: bone marrow, adipose tissue, cord blood and cord. We pay especial attention to quality control of cultures. The most interesting for us fields of MSC application are autoimmune diseases (multiple sclerosis, diabetis, Chrone disease), regenerative therapy (toxic hepatitis) and traumatology. In this field we carry out limited clinical trials. Also we investigate influence of MSC on allergic reactions. Here we at the stage of in vitro studies. And we’ve shown following effects after coculture of MSC and allergen activated lymphoceted: on the one hand decreasing of level of main trigger of allergic reaction – IL4, relative number of activated T cells and level of IgE. And on the other hand we observed increasing of anti-inflammatory cytokine IL10 and relative number of regulatory T cells. So after model of stopping of allergic reaction we are planning preclinical and limited clinical trials of application MSC for therapy resistance atopic asthma. Also we have good result of limited clinical trials of MSC in traumatology for difficult bone fracture, including in geriatric patients. Also we carry out limited clinical trials of autological MSC transplantation for arthritis and arthrosis treatment. The second big field of our work – is transplantation of allogenic fibroblasts for patient with extensive burns. All fibroblasts cultures passed strict quality controls and certified. We developed good for use dosage form based on fibroblasts culture in hydroxyethyl cellulose gel.

44

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Bioartificial Replacements of Blood Vessels – a Review Lucie Bačáková Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4 - Krc, Czech Republic; E-mail: [email protected]

Bioartificial tissue replacements comprise two main components: artificial material and cells. The artificial material acts as a carrier for the cells since they are generally anchorage-dependent. In advanced tissue replacements, the material component should not only to be passively tolerated by the cells but it should actively promote the adhesion, growth, differentiation, phenotypic maturation and other cell functions in a controllable manner. In other words, the material component should act as an analogue of the native extracellular matrix. In the first part of our research, we concentrated on the innovation of synthetic polymeric vascular prostheses used in the current clinical practice. These prostheses contain only the material component, and originally they have not been designed for the adhesion and growth of cells, particularly endothelial cells, although it is known that the confluent and mature endothelial cell layer is the best prevention of the prosthesis restenosis and failure. Therefore, the inner surface of knitted polyethylene terephtalate protheses was modified by special assemblies of extracellular matrix molecules (collagen, fibronectin) and particularly fibrin, because fibrinogen could be isolated in considerable amount from the patient´s own blood. These assemblies improved the cell-matrix and cell-cell adhesion of vascular endothelial cells, their subsequent growth and phenotypic maturation, and also their resistance to laminar shear stress generated by a perfusion cultivation system. In addition, the modified prostheses proved as functional when implanted in vivo, namely into minipigs. In the second part of our research, we focused on the creation of a completely new bioartificial vascular tissue. For this purpose, a polylactide-based biodegradable material carrier was applied. On the surface of these scaffolds, RGD-containing oligopeptides, i.e. ECM-derived ligands for integrin adhesion receptors on cells, were tethered through polyethylene oxide (PEO) chains. The concentration of these ligands on the material surface regulated the number of initially adhered endothelial and vascular smooth muscle cells (VSMC), the size of their spreading area and their proliferation activity. For example, on surfaces where the 5% of the PEO chains were functionalized with the RGD-oligopeptides, the VSMC adhered in lower number, but their spreading area was larger than on surfaces with 20% of PEO-RGD. On the other hand, the cell proliferation on surfaces with the higher RGD concentration was faster. It can be concluded that both tested material types supported the adhesion and growth of vascular endothelial and smooth muscle cells, and thus they are suitable for the reconstruction of tunica intima and tunica media on vascular prostheses. Materials functionalized with adhesion oligopeptides enable adhesion and growth of cells in a controllable manner. Supported by the Grant Agency of the CR (grants No. P108/11/1857 and P108/10/1106).

45

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Aortic Heart Valve Replacements Elena Filova1, Lubica Stankova1, Adam Eckhardt1, Hynek Chlup2, Lukas Horny2, Eva Gultova2, Jan Vesely2, Frantisek Straka1,3, Lenka Šimčíková1, Jana Musílková1, Jaroslav Masin3, Yuan-Tsan Tseng4, Jan Pirk3, and Lucie Bacakova1 1 Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic, 2Faculty of Mechanical Engineering, Czech Technical University in Prague, Czech Republic, 3Institute for Clinical and Experimental Medicine, Prague, Czech Republic 4Biomaterials Group, Department of Materials, University of Oxford, Oxford, UK

A considerable amount of patients need heart valve replacements worldwide. Mechanical prostheses, based on carbon, metallic and polymeric components, require permanent anticoagulation treatment, and their usage often leads to adverse reactions, e.g. thrombo-embolic complications and endocarditis. Xenogenous and allogenous biological prostheses are associated with immune reaction, thrombosis and degeneration, and thus they have a high rate of reoperation. Biological prostheses of autologous origin, such as pulmonary autografts, often burden the patient with a complicated surgery and risk of reoperation. New approaches involve development of bioartificial heart valve prostheses using scaffolds seeded with autologous cells in bioreactor, modification of biological tissues such as bovine or human pericardium with various cross-linking agents followed by seeding them with patient`s cells. The newly prepared bioartificial heart valve prostheses should be biocompatible, durable, endowed with appropriate mechanical properties and able to grow with a child. Chemical treatment of pericardium of bovine origin has been studied extensively. We evaluated a collagen scaffold and native human pericardium as a potential autologous tissue source in dynamic experiments. In addition, human pericardium was treated with various crosslinking agents and the effectiveness of cross-linking was assessed. Supported by the Grant Agency of the CR, grants No. P108/11/1857, P108/12/1168, P108/12/G108, P108/10/1106, and by the Ministry of Health of the Czech Republic, grant No. NT11270 – 4/2010.

46

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Clinimacs Prodigy in Regenerative Medicine Ivan Hutňan Miltenyi Biotec, Slovensko

Cellular therapies are being investigated for an increasing range of applications. Miltenyi Biotec has developed an integrated cell-processing system to perform all steps from sample preparation to final formulation of the cellular product Once safety and efficacy of a cell therapy product have been shown within a clinical trial program, successful commercialization may often be hampered by complex and costly production processes.. The CliniMACS Prodigy with its integrated fluid transfer, centrifugation, incubation and magnetic separation capabilities, has been designed for fully automated cell processing and cell culture applications. This GMP-compliant device is designed to be used with specialized CliniMACS Prodigy Tubing Sets which allow for a sterile and functionally closed fluid path.

47

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Legislativní rámec oboru Regenerativní medicína v ČR a EU RNDr. Eva Matějková Národní Centrum Tkání a Buněk a.s., Brno

Regenerativní medicína je zcela novým oborem, jehož historie se začala psát na konci 20. století. Evropská unie (a následně i Česká republika) trend rychle zaznamenala a svými aktivitami podporuje tuto oblast finančně, politicky i různými vzdělávacími činnostmi. Vzhledem k tomu, že Regenerativní medicína v sobě spojuje dvě rozsáhlé oblasti, a to farmaceutickou problematiku a problematiku týkající se použití lidských tkání a buněk, vyvstala potřeba vymezit legislativní rámec celého oboru. Přednáška se bude věnována vývoji právních předpisů regulujících Regenerativní medicínu, současnému stavu i odlišnostmi příslušné legislativy napříč státy Evropské unie.

The Legislative Framework for Regenerative Medicine in the Czech Republic and the EU Eva Matějková National Cell and Tissue Centre, Brno, Czech Republic

Regenerative Medicine is a brand new field of study which originated in the late 20th century. The European Union (and subsequently also the Czech Republic) became quickly aware of the trend and has been supporting this area with its financial, political and various educational activities. Because Regenerative Medicine encompasses two extensive areas, i.e., pharmaceutical issues and issues concerning the use of human tissues and cells, the need to define the legislative framework of the entire field arose. This lecture will focus on the development of legal regulations governing Regenerative Medicine, the current situation and differences between the corresponding laws across the individual states of the European Union.

48

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Transplantace allogenního štěpu sterna k uzávěru post-sternotomických defektů hrudní stěny – výsledky 4 let úspěšné mezioborové spolupráce Martin Kaláb Kardiochirurgická klinika Fakultní nemocnice Olomouc a Lékařská fakulta Univerzity Palackého Olomouc

Dehiscence sternotomie se vznikem rozsáhlého defektu hrudní stěny představuje život ohrožující komplikaci původně úspěšného primárního kardiochirurgického výkonu. Mortalita tohoto závažného stavu obvykle dosahuje až 70 %. Moderním způsobem léčby sternálních dehiscencí je použití AO dlahové osteosyntézy. V případech ztrátových defektů hrudní stěny je však tato metoda zatížena rizikem selhání vlivem destrukce nedostatečně ukotvených dlah. Inspirováni zkušenostmi ortopedické chirurgie jsme se rozhodli provádět náhrady těchto defektů pomocí allogenního kostního štěpu sterna. Ve spolupráci s Národním centrem tkání a buněk se podařilo vyvinout zcela novou a ojedinělou operační techniku. Ve sdělení je popsán její zrod, vývoj a také zkušenosti praktického použití za období 4 let vzájemně přínosné mezioborové spolupráce.

Transplantation of allogeneic sternal bone graft for closure of post sternotomy chest wall defects – results of four years of successful interdisciplinary collaboration Martin Kaláb Department of Cardiac Surgery University Hospital and Faculty of Medicine Palacky University, Olomouc, Czech Republic

Dehiscence of the sternotomy resulting in a large defect of the thoracic wall represents a life-threatening complication of an originally successful primary cardiac surgery procedure. Mortality rate of this serious condition is usually up to 70%. The use of AO plate osteosynthesis represents a modern approach to treatment of sternal dehiscences. In the case of chest wall loss defects, this method brings, however, a risk of failure due to destruction of insufficiently anchored plates. Inspired by orthopedic surgery experience, we have decided to repair these defects using sternal allogeneic grafts. In cooperation with the National Cell and Tissue Center, we have succeeded in developing a completely novel and rare surgical technique. Its origin, development, and also practical use experience gained during the 4-year period of mutually beneficial interdisciplinary cooperation, are described in the communication.

49

SBORNÍK ABSTRAKT / ABSTRACT BOOK

Skin Banking - Current Products and Future Developments C.D. Richters Euro Tissue Bank, division Euro Skin Bank, Beverwijk, The Netherlands

Allogeneic skin grafts are still important and even life saving for the treatment of severely burnt patients. Allogeneic skin is used as a temporary dressing, for final wound closure autologous skin is needed. Several methods have been developed to store the allogeneic skin until use, most often used are cryo-preservation and storage in high concentrations of glycerol (85%). With the clinical protocols now it is possible to save patients with large burns but the remaining scars can cause many difficulties, ranging from scar contraction to psychological disorders. The development of methods to decellularize human skin resulted in acellular dermal tissue for the treatment of deep burns or other full thickness wounds. Since all donor cells are removed, the remaining collagen-elastin matrix can be used as an implant, covered with a thin autologous split skin. Rejection will not take place and the donor dermal tissue will serve as a matrix for host fibroblast and blood vessels. Slowly, the donor collagen and elastin fibres will be replaced, leading to better scar quality. We have used a method with low concentrations of NaOH to decellularize allogeneic skin. This acellular dermis (Glyaderm) has been clinically investigated since 2005. The results show significant improvement of the elasticity of the scar, 1 year after the application of Glyaderm. Long term results up to 8 years show further improvement of scar quality. In combination with negative pressure wound therapy, Glyaderm can also be used for chronic wound treatment. Wound closure can be difficult in patients with extended wounds. Several techniques have been developed to expand the harvested autologous skin, such as Meek-Wall islands. The results of these techniques with respect to scar quality can be disappointing, probably caused by the longer period till wound closure is achieved. To speed up reepithelisation, cultured keratinocytes can be added to the wound, either allogeneic or autologous. Unfortunately, these techniques are expensive and the expansion of autologous cells in vitro takes often 2–3 weeks. Attempts to use foetal skin cells for this purpose have been made but ethical problems may arise. A future possibility may be the development of a living skin substitute constructed during operation of the patient, comprising both the epidermis and a dermal matrix populated with fibroblasts and endothelial cells.

50

SBORNÍK ABSTRAKT / ABSTRACT BOOK

The use of modern technologies in processing of human tissue products for clinical use Ján Karkoška National Cell and Tissue Centre, Brno, Czech Republic

Objective: Different methods are used for processing of tissues using different technologies all around the world. Since the adoption of Czech national regulation regarding human tissues and cells - Act 296/2008 Coll. (tissue and cells act) and decree 422/2008 Coll. the situation in the Czech Republic has changed radically. It was necessary to deal with the fundamental requirements of the new strict legislation, and conditions required by State inspection for drug control. Author describes development of new technological device intended for processing of human tissues, based on principles of isolator technology, in which product is hermetically closed and processed in super aseptic space (class A) and separated from the operators. Lecture is focused on processing of musculoskeletal tissues which is principally one of the most complex technological problems of musculoskeletal banking. The core problem primarily lies in operations which produce extreme quantities of particles, critical procedures are cutting and shaping of material using bone cutters, reamers and flushing technology. These operations distort purity of clean rooms. One way to solve the problem of these operations is based on using of isolator technology.

51

ZDRAVOTNICKÉ NOVINY

On-line fórum zdravotnictví a sociální péče

ODBORNÉ FÓRUM ZDRAVOTNICTVÍ

A SOCIÁLNÍ PÉČE www.zdravky.cz 63
r
číslo 5
r
24. února 2014 ISSN 0044-1996 cena 26 Kč r pro předplatitele 20 Kč

SÚKL vede krizový manažer

www.zdravky.cz

Z OBSAHU ■

Ministr zdravotnictví MUDr. Svatopluk Němeček, MBA, v pondělí 10. února odvolal z funkce šéfa Státního ústavu pro kontrolu léčiv MUDr. Pavla Březovského, MBA. Dočasným řízením ústavu pověřil PharmDr. Zdeňka Blahutu. Podle oficiální tiskové zprávy ministerstva zdravotnictví je důvodem odvolání MUDr. Březovského nespokojenost se způsobem řízení SÚKL, zejména v oblasti cenové a úhradové regulace, nedostatky v dozorových činnostech a nedostatečná kontrola nakládání s veřejnými prostředky. „Dosavadní výkony a styl práce úřadu se výrazně rozchází s mými požadavky na klíčovou instituci českého zdravotnictví. Ta by měla být pružnější a pod větší kontrolou státu. Současně považuji za nešťastné, aby jeden člověk řídil dvě významné instituce zároveň (pozn. ( red.: P. Březovský je od prosince r. 2006 ředitelem Koordinačč ního střediska transplantací, do funkk ce ředitele SÚKL byl 2. května 2012 jmenován ministrem doc. MUDr. Leošem Hegerem, CSc.). Pavlu Březovskému děkuji a přeji mnoho úspěchů v příštím působišti,“ uvedl ke svému rozhodnutí Svatopluk Němeček. Jako hlavní úkoly dočasného ředitele ministr stanovil zvýšení efektivity v oblasti cenové a úhradové regulace a urychlení správních řízení. Dále důslednou kontrolu vynakládání veřejných prostředků v činnostech SÚKL. „Největší důraz budu klást na precizní výkon regulace cen a úhrad, která povede k finančním úsporám pro pacienty a pro systém veřejného zdra-

votního pojištění,“ konkretizoval v tiskové zprávě MUDr. Němeček.

■

První prezentace ředitele PharmDr. Zdeněk Blahuta uspořádal den po svém jmenování briefing. Oznámil, že z titulu pozice krizového manažera s okamžitou platností provedl personální změny – odvolal náměstka pro odborné činnosti Mgr. Filipa Vrubela, náměstka pro ekonomiku Ing. Petra Noska a náměstka pro informační technologie Ing. Pavla Veselého. Konkrétní jména lidí, které přijme do svého týmu, slíbil oznámit do několika dnů. Zástupcům médií potvrdil Z. Blahuta priority svého působení v SÚKL, plynoucí ze zadání ministra. Za další svůj cíl pak stanovil zintenzivnění a zkvalitnění dozorových činností, které ústav provádí. Oznámil, že sdílí s ministrem zdravotnictví nedůvěru k některým případům vynakládání veřejných prostředků v činnosti ústavu, a neprodleně proto zadává provedení forenzního auditu (jak známo, v SÚKL aktuálně probíhá i ministerr ská kontrola). Prověřovány budou například některé zakázky v oblasti informačních technologií, dvacetimiliónová zakázka na služby public relations atd. V případech, ve kterých je to možné, vypisování dalších zaká-

22 × ročně, 590 Kč www.zdravky.cz

LÉKAŘSKÉ LISTY

ODBORNÁ PŘÍLOHA ZDR AVOTNICK ÝCH NOVIN

■

ISSN 0044–1996 24. února 2014 Ʉ www.zdravky.cz

2/2014

4/14

KONGRESOVÝ LIST ODBORNÁ PŘÍLOHA ZDR AVOTNICK ÝCH NOVIN

3. února 2014 Ʉ www.zdravky.cz Ʉ ISSN 0044-1996

1/2014

4 × ročně, 600 Kč www.urologickelisty.cz

florence duben 2014 / ročník X 60 Kč, 2,90 € / www.florence.cz

Otorinolaryngologie

XII. ČESKÉ A SLOVENSKÉ SYMPOZIUM O ARYTMIÍCH A KARDIOSTIMULACI

zek nový ředitel prý zatím pozas PharmDr. Blahuta také sdílí s no ministrem názor, že předcházejíc dení SÚKL nedostatečně řešilo blematiku reexportu léků, a bude věci věnovat zvýšenou pozornost prý informace o tom, že dochá k porušení zákazů vývozu léků, k vydal ministr MUDr. Martin Ho MBA. Možnost předcházení rizik exportu vidí nový šéf SÚKL napří v tom, že ústav bude sledovat tre výrobních výpadků a omezení k

Karcinomy v oblasti hlavy a krku | Etiologie | Příznaky a diagnostika | Souvislost s lidským papilomavirem | Chirurgické řešení | Systémová terapie Ʉ Rinosinusitidy | Současný pohled na diagnostiku a terapii Ʉ Hyperkinetická dysfonie | Současné postupy diagnostiky a terapie Ʉ OTC v otorinolaryngologii | Volně prodejná léčiva hrají v léčbě onemocnění stále větší roli

■

26.–28. ledna České Budějovice

s. 8 / Rozhovor

s. 12 / Odborné téma

s. 28 / Výzkumné sdělení

s. 38 / Z konferencí

ŽIVOT S ROZŠTĚPEM SE ZMĚNIL. MEDICÍNA POKROČILA A PACIENTI MAJÍ PŘÍSTUP K POTŘEBNÝM INFORMACÍM

PÉČE O DĚTSKÝ CHRUP

FLUKTUACE SESTER VE ZDRAVOTNICKÝCH ZAŘÍZENÍCH

INSPO 2014 LETOS PŘILÁKALO STOVKY NÁVŠTĚVNÍKŮ

PragueONCO 2014

Článek deníku MF Dnes ze 4. února nadepsaný „Tajná zpráva: Jak mizí miliardy z nemocn okamžitě vyvolal značnou pozornost – jeho obsahem je totiž poměrně důrazné naznačení v českých nemocnicích dochází k finančním nekalostem.

22.–24. ledna časopis obsahuje recenzované články

Praha

ské Vinohrady a ve fakultních nemocnicích v Olom a v Hradci Králové. Nejvíce prý na bonusech inkasovala vinohradská nem nice, jen od dodavatelů kardiostimulátorů a kardiover to před třemi lety činilo 95 miliónů Kč. Podle deníku popisuje protokol NKÚ, jak se manažeř mocnice v letech 2010 a 2011 dohodli se třemi dodávají firmami. „Nabídli jim bez výběrového řízení rámc smlouvy, zároveň se s firmami dohodli na vysokých cen Podle protokolu mnohdy přesně odpovídaly maximál cenám, které v daném roce slíbila platit VZP. V rámcov smlouvách byl zároveň stanoven bonus až do výše tří tin ceny dodávaného materiálu. Rozdíl mezi úhradou a běžnou cenou na trhu inkasovala nemocnice,“ uvádí nek. Autor pak sděluje, že protokol NKÚ sice popisuje krétní smlouvy fakultních nemocnic a přesně vyčís částky, které v letech 2010 a 2011 na bonusech inkaso – ale z důvodu ochrany obchodního tajemství nemo být zveřejněny. „Opatrnost NKÚ při publikaci zřejmě spěla k tomu, že podivná praxe neskončila,“ konstatu

ODBORNÉ TÉMA

Stomatologie

8. SYMPOZIUM PRACOVNÍ SKUPINY PLICNÍ CIRKULACE ČKS

Nová indikace – PDE 5 inhibitory – léčba erektilní dysfunkce a LUTS Ureterální stenty – nové možnosti ovlivnění nežádoucích účinků Guidelines EAU – zakřivení penisu

17.–18. ledna

Lži bez znalosti systému?

Na tiskové konferenci v pražském Faustově domě o „bonusové problematice“ hovořili (zleva) J. Kunová, D. Jurásková,

1 2013 11. ročník

ODBORN Ý Č A SOPIS PRO OŠE T ŘOVAT EL S T VÍ A OS TAT NÍ ZDR AVOT NICK É PROF E SE

Nemocnice se brání: Obchodn bonusy nejsou nemravné! Autor zmíněného článku záležitost shrnuje takto: „Nejde o složitý trik. Nemocnice nakoupí předražený materiál, který vyúčtují VZP nebo jiné pojišťovně. Od dodavatelské firmy si pak vyžádají vysoké bonusy, které často překračují polovinu fakturované ceny.“ O několik řádků dále pak doplňuje: „Nemocnice však může peníze použít libovolně, bez kontroly zdravotních pojišťoven. Třeba na právní nebo poradenské služby, což jsou nejčastější způsoby, jak vyvádět veřejné peníze do soukromých rukou.“ MF Dnes se odvolává na neveřejnou část protokolu, který sepsal Nejvyšší kontrolní úřad (NKÚ) po kontrole ve čtyřech státních zdravotnických zařízeních – pražských Všeobecné fakultní nemocnici a Fakultní nemocnici Králov-

10 × ročně, 570 Kč www.fl orence.cz

Důrazná reakce na inkriminovaný článek přišla z Aso ce nemocnic ČR (AN ČR) ještě v den jeho vydání: „Fak ní nemocnice odmítají článek vyvolávající představu popisovaný systém bonusů, který praktikuje většina mocnic, lze označit za nestandardní nebo dokonce, jak z článku vydedukovat, za odsouzeníhodný.

Špindlerův Mlýn

6 × ročně, 750 Kč www.csnn.eu

6 × ročně, 540 Kč www.eonkologie.cz

6 × ročně, 690 Kč www.kardiologickarevue.cz

6 × ročně, 600 Kč www.csgh.info

T H E J O U R N A L O F T H E C Z E C H A N D S LOVA K O N CO LO G I C A L S O C I E T I E S

‡„”—ƒ”›͸Ͷͷͺ ‘Ž—‡ͼ; —„‡”ͷ

K ARDIOLOGICK Á

ČESKÁ A SLOVENSKÁ

revue

KLINICKÁ ONKOLOGIE

NEUROLOGIE A NEUROCHIRURGIE

ͷ;ͶͺǦͽ;ͽͺȋ”‹–Ȍ ͷ;ͶͺǦ;Ͷ͹ȋǦŽ‹‡Ȍ

Gastroenterologie a hepatologie

IN TERNÍ MEDICÍNA

ƒ•–”‘‡–‡”‘Ž‘‰›ƒ†‡’ƒ–‘Ž‘‰› ,ƒ•‘’‹•,‡•±‰ƒ•–”‘‡–‡”‘Ž‘‰‹…±•’‘Ž‡«‘•–‹ǡ,‡•±Š‡’ƒ–‘Ž‘‰‹…±•’‘Ž‡«‘•–‹ǡ Ž‘˜‡•‡Œ‰ƒ•–”‘‡–‡”‘Ž‘‰‹…‡Œ•’‘Ž‘«‘•–‹ƒŽ‘˜‡•‡ŒŠ‡’ƒ–‘Ž‘‰‹…‡Œ•’‘Ž‘«‘•–‹ ›†ž˜ž, Ȃ‹†‡š‡†‹ǡ  ǡ Ȁǡ ǡ  –‘‹†‡šǡ ‘‘†…‹‡…‡ƒ†‡…Š‘Ž‘‰›„•–”ƒ…–•ǡ‹„Ž‹‘‰”ƒ’Š‹ƒ‡†‹…ƒ,‡…Š‘•Ž‘˜ƒ…ƒ

K A R D I O LO G I E

ČASOPIS ČESKÉ NEUROLOGICKÉ SPOLEČNOSTI ČLS JEP, ČESKÉ NEUROCHIRURGICKÉ SPOLEČNOSTI ČLS JEP, SLOVENSKEJ NEUROLOGICKEJ SPOLOČNOSTI SLS, SLOVENSKEJ NEUROCHIRURGICKEJ SPOLOČNOSTI SLS A ČESKÉ SPOLEČNOSTI DĚTSKÉ NEUROLOGIE ČLS JEP

Invazivní léčba karotických stenóz Trvalá kardiostimulace z pohledu nových evropských doporučení roku 2013 Kardiohepatální syndrom u chronického srdečního selhání Renální denervace – budoucnost nebo zklamání

MINIMONOGRAFIE

Chirurgická léčba hydrocefalu

V. Vybíhal

INTERNÍ MEDICÍNA

Chronické onemocnění ledvin – novinky Ledviny a gravidita Akutní poškození ledvin – klasifikace, přehled

PŘEHLEDNÝ REFERÁT

Upozornění na klasifikační, terminologické a obsahové inovace Mezinárodní klasifikace bolestí hlavy (ICHD-3 beta) pro primární bolesti hlavy

J. Opavský

Z obsahu:

PŮVODNÍ PRÁCE

Chirurgická liečba metastáz a jej vplyv na prognózu u pacientov s metastatickým kolorektálnym karcinómom

Validita Montrealského kognitivního testu pro detekci mírné kognitivní poruchy u Parkinsonovy nemoci O. Bezdíček et al

Na MRI založené 3D plánování brachyradioterapie karcinomů děložního hrdla – naše zkušenosti s použitím uterovaginálního aplikátoru Vienna Ring MR- CT

KRÁTKÉ SDĚLENÍ

Význam elektromyografie v chirurgické rekonstrukci spasticity horní končetiny

I. Čižmář et al

Significant Anti-tumor Effectiveness of Imatinib in C-kit Negative Gastrointestinal Stromal Tumor – Case Report

KAZUISTIKA

Stiff-Person Syndrome Associated with Myotonic Dystrophy type 2 – a Case Report E. Ehler et al

2,A Vydává ČLS JEP. ISSN 1210-7859. ISSN pro on-line přístup 1802-4041. Indexováno/excerpováno: Thomson Reuters Web of Knowledge: Journal Citation Report, Web of Science, Index Copernicus, EMBASE/Excerpta Medica, Bibliographia Medica Čechoslovaca, Scopus

ročník 77 | 110 | 2014 | číslo

|„•–”ƒ–ƒœ ƒ•–”‘ˆ×”ƒ͸Ͷͷͺ

1

Vydává ČLS JEP. ISSN 0862-495X. ISSN 1802-5307 on-line přístup Indexed in MEDLINE/PubMed, EMBASE/Excerpta Medica, EBSCO, SCOPUS, Bibliographia medica čechoslovaca, Index Copernicus

ročník 27 | 2014 | číslo

1

1

2014 / ročník 16

10 × ročně, 855 Kč www.artcasopis.cz 04

1 990 Kč www.artplus.cz

duben 2014

95 Kč / 4,50 ¤

Výstava Josefa Šímy na Kampě Rozhovor s Milošem Šejnem 34 / Fenomén českého linorytu

ƒŽ‰”ƒ—Ž‹— | ƪ‹š‹ƒ„ƒ’‘‘’‡”ƒ«À‘’Ž‹ƒ…‡—  ƒ†‹ƒ«Àœž–³ā’ƒ…‹‡–õ• |Ǧ •ƒ‘•–ƒ–ýˆ‡‘–›’ ”‘Œ‡–‹•‹‰–ƒ”•| ƒ•–”‘ˆ×”—͚͙͘͜

10 / 26 /

1 × ročně, 139 Kč www.artplus.cz Ročenka únor 2014 | cena 139 Kč, 6,20 € | www.artplus.cz

ROČENKA 9 771213 839008

04

trh s uměním v roce 2013

Vyberte si... 52

www.ambitmedia.cz

53

KONTAKTY / CONTACTS

Národní Centrum Tkání a Buněk a.s. – Campus Science Park Palachovo náměstí 726/2, 625 Brno, České Republika www.natic.cz; [email protected]

PrimeCell Therapeutics a.s. Jáchymova 26/2 110 00, Praha 1, Česká republika www.primecell.cz; [email protected]

54

BLOCK® GROUP Sdružení společností BLOCK® GROUP představuje silnou mezinárodní skupinu na trhu dodavatelů investičních celků. BLOCK® GROUP poskytuje komplexní služby v projektové přípravě, výrobě a výstavbě investičních celků s náročnými technologiemi a vysokou kvalitou prostředí (čisté prostory). Pro tyto celky rovněž zajišťuje následný servis a validace. Aktivní činnost vyvíjí ve střední Evropě a Rusku. BLOCK® působí v oblastech:

Farmacie a biotechnologie

Zdravotnictví

Komplexní dodávky stavebních a technologických celků pro oblast farmacie a biotechnoogie

Komplexní dodávky investičních celků pro zdravotnictví

Věda a výzkum

Izolátorová technologie

Dodavatel komplexních laboratoří pro vědu a výzkum

Izolátory šité na míru

Izolátorová technologie BLOCK ® Flexibilní modulární řešení izolátorové technologie, zakázková výroba izolátorovétechnologie. Hlavní výhody: • • • • • • •

Jsme lídry a průkopníky izolátorové technologie ve východní Evropě Kvalitu našich výrobků podporují 22leté zkušenosti Špičková kvalita za zajímavou cenu Výrobek na míru - určujete si podobu izolátoru od samého počátku Leštěný povrch - snadnější čištění a dekontaminace Možnost integrace dalšího vybavení Komplexní péče od objednávky, přes vývoj až po provozní podporu

Sídlo firmy: BLOCK a.s., Stulíková 1392, 198 00 Praha 9 Korespondenční adresa: BLOCK a.s., U kasáren 727, 757 01 Valašské Meziříčí Tel.: +420 571 670 111 Fax: +420 571 670 244 E-mail: [email protected]

w w w. bl o c k . cz

ç)ë)2Ž 463/%ö(ž/63/ &92ËÅ2Š8)6%4-)

Z¾LVEHR®QHMWXVMFYXSVIQTVSHYOXð1EGSTLEVQE NIWTSPIÆRSWX:-:%'31WVS www.vivacom.cz/macopharma :-:%'31WVS`/V¢PSHZSVWO¢4VELE`8IP`)QEMPZMZEGSQ$ZMZEGSQG^