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

Transkript

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

2 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 H 2 O 2 Systém odpovídá vysokým nárokům na hygienickou nezávadnost, snadnou čistitelnost a desinfikovatelnost Sídlo firmy: BLOCK a.s., Stulíková 1392, Praha 9 Korespondenční adresa: BLOCK a.s., U kasáren 727, Valašské Meziříčí Tel.: Fax: block@block.cz

3 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

4 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

5 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

6 Hlavní témata Konference 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 Conference Main Topics 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

7 Partneři konference Conference Partners Generální partner Hlavní partner Stříbrný partner Bronzový partner Mediální partneři Media partners 5

8 PROGRAM KONFERENCE / CONFERENCE PROGRAM Program konference Conference Program Středa, 9. dubna Wednesday, April Registrace účastníků Participants registration Slavnostní zahájení konference Welcome speech to the Conference 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 Coffee break 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

9 PROGRAM KONFERENCE / CONFERENCE PROGRAM Oběd / Lunch 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 Coffee break 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) 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 7

10 PROGRAM KONFERENCE / CONFERENCE PROGRAM Čtvrtek, 10. dubna Thursday, April 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 Coffee break 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 Oběd/Lunch 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 Coffee break 8

11 PROGRAM KONFERENCE / CONFERENCE PROGRAM 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 Závěr konference / The end of Conference 9

12 10

13 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, kucera@block.cz, block@block.cz 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, kucera@block.cz, block@block.cz 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: ep@eproznov.cz 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: ep@eproznov.cz 11

14 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, info@hpst.cz 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, info@hpst.cz. 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: , mail: spacil@merci.cz 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 spacil@merci.cz 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, radim.kviatkovsky@morys.cz 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, radim.kviatkovsky@morys.cz 12

15 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: mail@trigon-plus.cz, tel 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: mail@trigon-plus.cz, telephone 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, vivacom@vivacom.cz 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, vivacom@vivacom.cz 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

16 14

17 SBORNÍK ABSTRAKT ABSTRACT BOOK 15

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

19 OBSAH / CONTENT Legislativní rámec oboru Regenerativní medicína v ČR a EU The Legislative Framework for Regenerative Medicine in the Czech Republic and the EU 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 Skin Banking - Current Products and Future Developments The use of modern technologies in processing of human tissue products for clinical use

20 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

21 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

22 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

23 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

24 Pluripotent Stem Cell-based Neural Disease Models Yuh-Man Sun Faculty of Medicine, the Department of Biology, Masaryk University, 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

25 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

26 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

27 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 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

28 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 ICRS- IKDC 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

29 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 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 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

30 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 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