Stem Cell Engineering

Transcription

1 Stem Cell Engineering

2

3 Gerhard M. Artmann Stephen Minger Jürgen Hescheler Editors Stem Cell Engineering Principles and Applications 123

4 Editors Prof. Dr. Gerhard M. Artmann Institute of Bioengineering and Centre of Competence in Bioengineering Aachen University of Applied Sciences Heinrich-Mußmann-Straße Jülich Germany artmann@fh-aachen.de Dr. Stephen Minger King s College London Wolfson Centre for Age-Related Diseases GKT School of Biomedical Sciences London United Kingdom SE1 1UL stephen.minger@kcl.ac.uk Prof. Dr. Jürgen Hescheler Universitätsklinikum Köln Inst. Neurophysiologie Robert-Koch-Str Köln Germany j.hescheler@uni-koeln.de ISBN e-isbn DOI / Springer Heidelberg Dordrecht London New York Library of Congress Control Number: We, the editors edited to the best of our knowledge. However we would like to emphasize, that the chapter authors are fully responsible for the contents of their articles, citations etc. Springer-Verlag Berlin Heidelberg 2011 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Cover design: WMXDesign, Heidelberg Printed on acid-free paper Springer is part of Springer Science+Business Media (

5 About the Authors Prof. Arti Ahluwalia, PhD She obtained her B.Sc. in physics and Ph.D. in bioengineering; Arti Ahluwalia is associate professor of bioengineering at the Faculty of Engineering, University of Pisa, and vice director of the Interdepartmental Research Center E. Piaggio. She is also affiliated with National Council of Research Institute of Clinical Physiology (CNR-IFC) and carries out part of her research activities within the laboratories of the Institute. Her main scientific interests are focused on the interaction between biological systems and man-made devices or structures. In this context, her research activities span from biomolecular films, bioreactors, surface engineering, and biosensing to microfabrication and biomaterials for tissue engineering. Omonigho Aisagbonhi, MD, PhD She is an M.D./Ph.D. graduate student in the Medical Scientist Training Program at Vanderbilt University Nashville, TN, USA. She obtained her B.Sc. in biochemistry from California State University, Long Beach, in v

6 vi About the Authors Prof. Dr. habil. Gerhard M. Artmann He studied physics at the Technical University of Dresden ( ). He obliged to leave East Germany in 1985 and became a Ph.D. student at RWTH Aachen ( ). Since 1989 he is a professor at Aachen University of Applied Sciences where he was a dean of the Faculty of Applied Physics ( ). He habilitated in 1999 at TU Ilmenau and is chair of the Center of Competence in Bioengineering since 2003 as well as managing director of the Institute of Bioengineering. Kuppusamy Aravindalochanan He has completed his bachelor of engineering in Madras University, India. He acquired his masters in biomedical engineering from University of Applied Sciences, Albstadt-Sigmaringen University, Germany. Since 2004, he is working as a scientist in Laboratory for Sensors, Department of Microsystems Engineering, Freiburg, Germany. His fields of interest are multi-physics simulation, MEMS, and electro-chemical sensor development for clinical and diagnostic applications. Prof. Andrew H. Baker He is a non-clinical professor in molecular medicine and the British Heart Foundation Glasgow Cardiovascular Research Centre at the University of Glasgow, Glasgow, UK. He specialized in vascular biology, gene therapy and, more recently, stem cell biology and the application of genetic engineering to manipulate human pluripotent stem cells.

7 About the Authors vii Prof. Christoph Becker, PhD He studied biology at the RWTH Aachen University, Aachen, Germany. In his Ph.D. studies he investigated regulation mechanisms of subcellular trafficking of glucose transporters in cardiomyocytes at both the Department of Physiology, Medical Faculty, RWTH Aachen University and the Department of Biochemistry and Molecular Biology, Biological Faculty, University of Barcelona. As a postdoc he joined the Interdisciplinary Center of Clinical Research BIOMAT at the University Hospital Aachen and the National Cancer Institute at the National Institutes of Health in Bethesda, MD, USA. Since 2003 CB is head of the laboratory of urology at the University Hospital Aachen. In several projects he investigates the myogenic differentiation potential of bone marrow stromal cell and develops collagenous biomaterials for the tissue engineering of urinary bladder and ureter, respectively. Dr. Anne Bernhardt Anne Bernhardt studied biochemistry at Martin-Luther University Halle-Wittenberg. She worked at the Max Planck Research Unit for Enzymology of Protein Folding in Halle and received Ph.D. in She is a member of the group Tissue Engineering and Biomineralization at the Max Bergmann Center for Biomaterials/Institute of Materials Science of Technical University, Dresden, Germany, since 2001.

8 viii About the Authors Paul R. Bidez III, PhD He earned his B.S. from West Chester University in 1997, his MBA from Pennsylvania State University in 2002, and his Ph.D. from Drexel University in He is also a Certified Six Sigma Black Belt. With funding from the National Aeronautics Space Administration (NASA) he completed his MBA working on novel pathways of stem cell differentiation. Upon completion of his Ph.D., he joined the Research Planning and Integration subdivision of Merck Research Laboratories, a division of Merck & Co, North Wales, PA, USA. Dr. Bidez currently applies Six Sigma and Change Management Methodologies to a variety of opportunities in the drug discovery and development processes. Thomas Brevig, MD, PhD He is director of Global Research in Labware & Speciality Plastics in Thermo Fisher Scientific, Roskilde, Denmark. He graduated in medicine in 1998 and received his Ph.D. in neuroscience in 2001, both from University of Southern Denmark. He has made scholarly contributions in the fields of transplantation immunology, brain repair, biomaterials, and cell culture and analysis. Melissa Brown, BSc, PhD She received a B.S. in bioengineering from Syracuse University in 2004 and a PhD in biomedical engineering from Duke University, Durham, NC USA in Her Ph.D. dissertation focused on cord blood-derived endothelial progenitor cells and their use in prevention of restenosis in vessels that have undergone various atherosclerosis treatment methods. She received fellowships from an Institutional Training Grant on Biomolecular and Tissue Engineering and the American Heart Association.

9 About the Authors ix Cindy Cheng, BSc She is a biomedical engineering graduate student studying under Dr. George A. Truskey at Duke University, Durham, NC, USA. Cindy received a B.S. in Biomedical Engineering from Duke University in She is a Fellow in the Center for Biomolecular and Tissue Engineering at Duke and is supported by an Institutional Training Grant from the National Institutes of Health. Matthew Dalby, PhD He is a lecturer in cell Engineering at the University of Glasgow, UK. He started the post in the Faculty of Biomedical and Life Sciences after completing a 5-year BBSRC David Phillips research fellowship. Prior to this he was a research assistant with Profs. Adam Curtis and Chris Wilkinson and Dr. Mathis Riehle and a Ph.D. student at the IRC in Biomedical Materials, Queen Mary College, University of London. His interests are bone cell engineering, nanotopography, and cell mechanotransduction; and he works within an interdisciplinary environment comprising biologists, orthopedic surgeons, and engineers. He has published around 60 papers and reviews. Bernd Denecke, PhD He studied biology at the Ruhr University Bochum and received his Ph.D. at the Institute of Cell Biology (Tumor Research), University of Essen Medical School. After his postdoctoral fellowship at the Institute of Medical Microbiology, Hannover Medical School (MHH), he started his work at the Interdisciplinary Center for Clinical Research on Biomaterials and Material Tissue Interaction of Implants BIOMAT of the RWTH Aachen, Germany. Since 2005 he is head of the Chip-Facility which he established at the Interdisciplinary Center for Clinical Research BIOMAT.

10 x About the Authors Lucia Denk, PTA Lucia Denk finished her apprenticeship as pharmaceutical technical assistant in Afterward she worked at a pharmacy. Since 2002 she has a position as technical assistant at the Institute of Cellular and Molecular Anatomy, University of Regensburg, Regensburg, Germany. Prof. Chris Denning He is an associate professor and reader in the Wolfson Centre for Stem Cells, Tissue Engineering and Modelling at the University of Nottingham, Nottingham, UK. His interests are in improving culture, scalability, cardiac differentiation, and transgenesis in human embryonic and induced pluripotency stem cells with a view to drug screening and in vitro modeling of genetic disease. Paolo Di Nardo, MD He is a cardiologist, directs the Laboratory of Cellular and Molecular Cardiology at the University of Rome Tor Vergata and is member of the Board of the National Institute for Cardiovascular Research (INRC), Italy. Scientific advisor of major international organizations and member of international scientific societies, he is author of several papers published in peer-reviewed international scientific journals. In 1994, he organized the First International Congress in which the possibility of heart regeneration in mammalians was analyzed. Since then, his major interests have been in stem cell and tissue engineering technology.

11 About the Authors xi Ilya Digel, PhD He was born in 1973 in Zhambyl (Kazakhstan). In 1995 graduated from Kazakh National University (biology and chemistry) in Almaty with a Diploma of Honors. He received his Ph.D. in microbiology from the same University (1998). Since 2001, he is research member in the Laboratory of Cellular Biophysics at Aachen University of Applied Sciences. He is leading a group working on molecular biophysics, microbiology, and cell biology. Rita R. Fiñones, PhD Rita Fiñones, Ph.D. candidate in Materials Science and Engineering, University of California at San Diego, CA, USA, is a graduate student in the laboratory of Dr. Martin Haas. Her dissertation is focused on developing a stem-cell-inspired model of prostate cancer progression. She is interested in the translation of stem cell concepts to the study of cancer and to the development of regenerative therapies. Lesley Forrester, PhD She received her Ph.D. in the clonal analysis of hematopoietic stem cells from the University of Edinburgh, Edinburgh, in 1986 and carried out postdoctoral training in Toronto, ON, Canada. She established her own group at Edinburgh University in 1994 where her work is focused on the production of hematopoietic cells from embryonic stem cells. Jane Frimodig, PhD Jane Frimodig is a Ph.D. candidate in materials science and engineering, currently working in the Department of Bioengineering at the University of California, San Diego, CA, USA. She received a master of science degree with distinction in materials engineering from California State University Northridge. In 2007 and 2008 Ms. Frimodig received the Chancellor s Collaboratories Grant, awarded to promote interdisciplinary collaborations.

12 xii About the Authors Andreas Geerts, Dipl. Biol. He received diploma in biology (1993) at the University of Cologne (genetics, biochemistry, pharmacology). Scientific work in Institut für Enzymtechnologie der Universität Düsseldorf, Max Planck Institut für Züchtungsforschung Cologne, and Centro National de Biotechnologia Universidad Autonoma de Madrid. Scientist at institute for target discovery at Bayer Schering Pharma AG, Wuppertal, Germany. Michael Gelinsky, PhD He studied chemistry at the Albert Ludwigs University in Freiburg (Breisgau) and did his Ph.D. in the field of bioinorganic chemistry. Since 1999 he is working at the Institute of Materials Science of Technical University in Dresden, Germany. Since 2002 he is head of the research group Tissue Engineering and Biomineralization which is located in the newly founded Max Bergmann Center of Biomaterials (Institute of Materials Science, Technical University, Dresden). He and his group focus on the development of new biomaterials, especially for bone and cartilage reconstruction, scaffold-based tissue engineering, novel methods for scaffold fabrication, and bone biomineralization. Stefan Golz, PhD He received Ph.D. in molecular biology (1999) at the University of Cologne (Institute for Genetics) about protein protein interactions of T4 endonuclease VII. He is senior scientist at the Institute for Target Discovery, Bayer Schering Pharma AG, Wuppertal, Germany.

13 About the Authors xiii Sabrina Gordon-Keylock, PhD She completed her Ph.D. in 2007 in Dr. Lesley Forrester s laboratory on the hematopoietic differentiation of murine embryonic stem cells and is currently carrying out her postdoctoral training in the Institute for Stem Cell Research at the University of Edinburgh, Edinburgh. David A. Gough, PhD He received his Ph.D. from the University of Utah in 1974 and was a postdoctoral fellow at the Joslin Clinic of the Harvard Medical School. He is a founding fellow of the American Institute of Medical and Biological Engineering and a recipient of the M. J. Kugel Award presented by the Juvenile Diabetes Foundation and the Jacobs School s Teacher of the Year Award in He is a former chair of the Bioengineering Department at UCSD, CA, USA. Marijke Grau, PhD She received master of science from the University of Bremen (Germany), in She recently completed her PhD at the RWTH Aachen University (Germany). She now continues with her postdoctoral research studies at the Institute for Molecular and Cellular Sports Medicine (German Sports University Cologne, Germany). She investigates the regulatory mechanisms of the red blood cell nitric oxide synthase and the physiological and pathophysiological relevance of the enzymatic synthesized nitric oxide.

14 xiv About the Authors Rylie Green, PhD She completed her Ph.D. in neural interfaces in the Graduate School of Biomedical Engineering, at the University of New South Wales, Australia, where she is now undertaking postdoctoral research studies. Her expertise is focused on the development of biosynthetic systems for improving the interactions of tissues at device interfaces. Dr. Green is a member of the Institute of Engineers, Australia, and the Australasian Society for Biomaterials and Tissue Engineering (ASBTE). Dr. Green has received a Fresh Science Award which recognises upcoming scientists throughout Australia. Rylie has also received the Ruldolf Cimdens Award from the European Society of Biomaterials and number of a international travel grants from ASBTE and UNSW. Martin Haas, PhD He received his B.Sc. degree in electrical engineering from the Technicon, Israel Institute of Technology and his Ph.D. in biophysics from the University of California, Berkeley, CA, USA. During his postdoctoral research at the Salk Institute, he worked on the DNA tumor viruses under the direction of Drs. Renato Dulbecco and Marguerite Vogt. As senior scientist at the Weizmann Institute and then as professor at UCSD, Dr. Haas studied radiation-induced leukemia in mice, followed by work in the tumor suppressor field. Based on his extensive experience in the areas of virology, cell biology and the use of gene transfer vectors, Dr. Haas recently entered the field of stem cell research. Prof. Antonis Hatzopoulos, PhD He is an associate professor of Medicine and Cell and Developmental Biology at Vanderbilt University, Nashville, TN, USA. He obtained his B.Sc. in chemistry from Aristotelian University of Thessaloniki, Greece, and his Ph.D. degree from Northwestern University, Evanston, IL, USA.

15 About the Authors xv Prof. Dr. med. Dr. h.c. Jürgen Hescheler He is Chairman and Director of the Institute of Neurophysiology at the University of Cologne. He has been working with embryonic stem cells of the mouse for over 20 years. Beginning with studies on cellular signal transduction, he has defined many important basic aspects both of fundamental research and of clinical applications. He was the first scientist worldwide to perform electrophysiological experiments on stem cells thus pioneering the establishment of stem cell research for application in transplantation medicine. In 2002 he was the first scientist in Germany to obtain permission to work with human hmbryonic stem cells. In March 2004 he was appointed coordinator of the European Consortium FunGenES (Functional Genomics of Engineered Embryonic Stem Cells) followed by CRYSTAL (Cryobanking of Stem Cells for human therapeutic application) in 2005 and ESNATS (Embryonic stem cell-based novel alternative testing strategies) in He is also coordinator of the BMBF consortium ips and adult bone marrow cells for cardiac repair, which started work in March In 2005 he founded the German Society for Stem Cell Research. Isgard S. Hueck, MSc Born in Germany, she studied biology at the Westfaelische Wilhelms University of Munster and received her license as cytopathologist in Cologne, Germany, in After many years of clinical work experience in hematology, cancer diagnosis, and therapy, she received a master of science degree in biomedical engineering at the Aachen University of Applied Sciences, Germany, in conjunction with the University of California, San Diego, CA, USA, in Based on her extensive expertise in the areas of cellular engineering, cytohistopathology, and cancer research, Isgard Hueck is a key connection between interdisciplinary and international cooperation in biomedical research. Her main research interests are in the studies of cellular cancer diagnosis, angiogenesis, and stem cells.

16 xvi About the Authors Prof. Gerhard Jakse, MD He studied medicine at the Medical Faculty of Graz. In several temporary employments at the New York State Hospital in Utica and Rochester and at Urology Departments in Klagenfurt, Linz, Innsbruck, Mainz, and Iowa City, he underwent professional training in both general medicine and urology. Following his venia legendi he became associate professor of urology at the University of Innsbruck and continued his career as full professor of urology at the Technical University of Munich and the RWTH Aachen University, Aachen, Germany. GJ is member of several national and international Urological Societies and collaborates in various Urological Journals. Nicole M. Kane, PhD She is a postdoctoral research associate at the British Heart Foundation Glasgow Cardiovascular Research Centre at the University of Glasgow. Her research is focused on the genetic manipulation of human embryonic and induced pluripotent stem cells to further delineate pluripotency and differentiation commitments, in particular to a cardiovascular lineage. Prof. Malte Kelm, MD He is university professor of medicine and chairmen of the Department of Cardiology, Pneumology, and Vascular Medicine University Hospital Düsseldorf (Germany). Beside his interests including interventional catheterization and cardiac imaging techniques, he has developed a profound expertise in the underlying mechanisms and therapy of coronary micro- and macroangiopathy with special focus on molecular mechanisms of endothelial dysfunction and nitric oxide pathways.

17 About the Authors xvii Stefanie Keymel, MD She studied at Heinrich-Heine University Düsseldorf and received M.D. for the investigation of EPC and endothelial dysfunction with aging. Medical and scientific education was obtained at the University Hospital Aachen (Germany) and since 2009 in the Department of Cardiology, Pneumology, and Vascular Medicine University Hospital Düsseldorf (Germany) and since 2009 in the Department of Cardiology, Pneumology, and Vascular Medicine University Hospital Düsseldorf (Germany). Research was focussed in the field of NO and microvascular biology. Jochen Kieninger studied physics and micro system technology at the University of Freiburg. He received his diploma in 2003 ( Dipl.-Ing. Mikrosystemtechnik. ). Afterwards he worked at the Laboratory for Sensors (Prof. Gerald A. Urban) in the field of electrochemical sensors, micro fluidics, and thin-film technology. Since 2008 he is head of the group Sensors for cell culture monitoring & micro technology he joined the School of Soft Matter Research of the Freiburg Institute for Advanced Studies (FRIAS) in the group of Prof. Andreas Manz. John Paul Kirton, PhD He received his B.Sc. in biochemistry in 2001 and a Ph.D. in molecular biology (2006) following studies at the Wellcome Trust Centre for Cell-Matrix Research, The University of Manchester. He then attained a postdoctorate position in vascular biology within the same department. His current postdoctorate research role is held at King s College London, UK, studying vascular and stem cell biology.

18 xviii About the Authors Petra Kleinbongard, PhD She studied biology and received the master of science 1999 from the Ruhr University Bochum (Germany). She has done her Ph.D. in biology in 2003 in cooperation between the Division of Cardiology, Heinrich-Heine-University Düsseldorf (Germany) and the Department of Biology, Ruhr University Bochum (Germany). Since 2003 she is postdoctoral fellow (Institute of Pathophysiology, University of Essen Medical School, Essen, Germany) and did research in the field of circulating blood, blood cell functions, and interactions with vascular cells. Frank Kloss He attended both Dental School at the University of Würzburg and Medical School at the University of Erlangen-Nürnberg, where he also started his medical career at the Department for Maxillofacial and Oral Surgery. From there, he moved on to the Medical University Innsbruck, Austria, to finish specialty training. He now holds a residency in oral-, maxillofacial surgery and guides various research projects focused on bone implantology and cancer. He is winner of the Scientific-Hans-Pichler-Award 2008 granted by the Austrian Society for Oral-, Maxillofacial Surgery. He is a research committee member of the International Bone Research Association (IBRA). Prof. Karl-Heinz Krause, MD He is professor of medicine at the University of Geneva. He has two major research interests: (i) oxidative stress and NOX family NADPH oxidases and (ii) neuronal differentiation and brain development, using pluripotent stem cells as models and tools. He is elected member of the Swiss Academy of Medical Sciences, as well as the American Society for Clinical Investigation.

19 About the Authors xix Prof. J. Yasha Kresh, PhD He is currently professor of cardiovascular medicine and surgery, research director of Cardiothoracic Surgery and Cardiovascular Biophysics Laboratory at the Drexel University College of Medicine, Philadelphia, PA, USA. He received his Ph.D. in biomedical (cardiovascular) engineering from Rutgers. He works at the interface of medicine and engineering, dedicated to the discovery and development of innovative methodologies for the treatment of system disorders. He is fellow of the American College of Cardiology, American Heart Association, American Institute for Medical and Biological Engineering, Biomedical Engineering Society and senior member of many biological, medical, and engineering organizations. He resides in Pennsylvania with his number one wife (Myrna) and their two black Labradors (Gidget and Melody) which do not retrieve. Prof. Peter I. Lelkes, PhD He is the Calhoun Chair Professor of cellular tissue engineering at Drexel University s School of Biomedical Engineering, Science and Health Systems (BIOMED) and honorary professor at the Changchun Institute of Polymer Chemistry and Physics, at Chinese Academy of Sciences, and at the Aachen University of Applied Sciences, Germany. Dr. Lelkes earned his Ph.D. in 1977 from the Technical University (RWTH) in Aachen, Germany. He joined Drexel University in 2000 after working for 5 years at the Weizmann Institute of Science (Rehovot, Israel), 5 years at the National Institute of Health (Bethesda, MD), and 12 years at the University Wisconsin.

20 xx About the Authors Prof. Günter Lepperdinger He was principal investigator and section head at the Institute for Biomedical Aging Research of the Austrian Academy of Sciences in Innsbruck, Austria, since He is an adjunct professor of biochemistry at the University of Salzburg and an adjunct professor of developmental biology at the University of Innsbruck. He is a recipient of the Christian-Doppler-Award, the Best of Biotechnology Award, and the Werner-Welzig-Award; he is an APART fellow of the Austrian Academy of Sciences, Burgen Scholar of the Academia Europeae, and Elected Life-Time Member of the International Society for Hyaluronan Sciences. He served as an associate editor for Experimental Gerontology Elsevier and he currently is section editor for Regenerative Medicine and Technology of Karger s international journal Gerontology. Dr. Anja Lode She studied biology (University Potsdam) and did Ph.D. in genetics (Technical University Dresden, 2001). She is a member of the group Tissue Engineering and Biomineralization at the Max Bergmann Center for Biomaterials/Institute of Materials Science of Technical University Dresden, Germany, since Penny Martens, PhD She is a lecturer in the Graduate School of Biomedical Engineering at the University of New South Wales, Australia. She obtained her PhD in Chemical Engineering from the University of Colorado in Her main research activities involve the development of biosynthetic polymeric hydrogel composites for use in biomaterial applications and the evaluation of their material and biological properties. She is currently serving as treasurer of the Australasian Society for Biomaterials and Tissue Engineering and is on the board of the Federation of Australian Scientific and Technological Societies. Penny has also been awarded a 2009 NSW Young Tall Poppy Science Award.

21 About the Authors xxi Dr. Stephen Minger He was appointed the Global Director for Research and Development for Cell Technologies at GE Healthcare in September Dr. Minger received his PhD in Pathology (Neurosciences) in 1992 from the Albert Einstein College of Medicine. After post-doctoral work in CNS gene therapy, neural transplantation and neural stem cell biology, he moved to the UK in 1996 and was appointed a Lecturer in Biomolecular Sciences at King s College London in Over the past 18 years, his research group has worked with a wide range of tissue-derived stem cell populations, as well as mouse and human embryonic stem (ES) cells. In 2002, his research team was awarded one of the first two licenses granted by the UK Human Fertilisation and Embryology Authority for the derivation of human ES cells and his group was the first to deposit a human ES cell line into the UK Stem Cell Bank. Minger was also one of the first two groups in the UK to be granted a research license by the HFEA in 2008 to pursue Somatic Cell Nuclear Transfer (SCNT) to generate hybrid human embryos for fundamental research into genetic forms of neurodegenerative conditions. Stephen is the Stem Cell Expert and a Member of the UK Gene Therapy Advisory Committee (GTAC) at the Department of Health and was until recently the Focal Point for Regenerative Medicine, Drug Discovery and Modernisation of Traditional Chinese Medicine for the UK Department of Business, Innovation and Skills in China. Marilena Minieri, PhD She is an experimental pathophysiologist, works at the Laboratory of Cellular and Molecular Cardiology, University of Rome Tor Vergata, and is senior scientist of the National Institute for Cardiovascular Research (INRC). She is author of several papers published in peer-reviewed international scientific journals. Her major scientific interests span from intracellular signaling to stem cell and tissue engineering technology.

22 xxii About the Authors Prof. Will W. Minuth He is a professor of anatomy at the University of Regensburg in Germany. He is teaching medical students in gross anatomy, histology, and neuroanatomy. The research interest is related to the field of renal epithelial barrier function including the action of steroidal hormones. The driving force in his experimental work is the unsolved question, if stem/progenitor cells can be applied in future to treat acute or chronic renal failure. For that reason the actual research of Dr. Minuth is focusing to renal stem/progenitor cells developing into a functional epithelium under the tubulogenic action of aldosterone. Sophisticated perfusion culture including an artificial interstitium plays an essential role in this hot spot of research. Katrin Montzka, PhD She studied bioengineering at the University of Applied Sciences in Aachen, Germany. She joined the Department of Genetics, Cell Biology and Anatomy, Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, USA, as a visiting fellow. In her Ph.D. studies she investigated the potential therapeutic application of human bone marrow-derived mesenchymal stromal cells in experimental spinal cord injury at the Department of Neurology, RWTH Aachen University. Employment followed as a Research Associate at the Department of Urology at the RWTH Aachen University, Germany. Guido Nikkhah, PhD He studied medicine in Giessen, Germany ( ) and received his Ph.D. degree in neurobiology from the University of Lund, Sweden (1994). He trained in neurosurgery in Hanover, Germany, where he also habilitated (1997). From , he was the vice-chairman of the clinical department of Stereotactic and Functional Neurosurgery and head of the research group Molecular Neurosurgery at the University of Freiburg, Germany. In 2007 he became the chairman of this department. He has also been the president and board member of NECTAR (Network of European CNS Transplantation and Restoration) and the treasurer of the Academia Eurasiana Neurochirurgica.

23 About the Authors xxiii Robert Nordon, PhD He obtained his medical degree and Ph.D. at the University of New South Wales (UNSW), Australia. Robert is currently working in the Graduate School of Biomedical Engineering at UNSW. His major research interest is the development of bioreactor technologies for the study and delivery of cell-based therapies. He is the inventor of hollow fiber cell separation and expansion device that has been commercialized for clinical application. His more recent work focuses on progenitor cell fate mapping and mathematical modeling of stem cell development. Prof. Richard Oreffo, PhD He holds the chair of musculoskeletal science and is co-founder of the Centre for Human Development, Stem Cells and Regeneration. He is associate dean for innovation and enterprise within the Faculty of Medicine, Health and Life Sciences, University of Southampton. Richard graduated from Liverpool and Oxford with degrees in biochemistry and a D.Phil. in bone biology. He leads a research group focused on understanding bone development and developing strategies to regenerate bone and cartilage using stem cell technology and innovative scaffolds for orthopedic application (see Much of the work is undertaken in multidisciplinary programs in collaboration with clinicians, bioengineers, modelers, and bone biologists. He has published over 120 peer-reviewed papers and 20 contributed reviews/book chapters. Burcin Özüyaman, MD He received his M.D. in the field of nitric oxide research with a special regard to its role in platelet function. He continued his research career at the Institute of Cardiovascular Physiology, Heinrich-Heine-University, Düsseldorf (Germany). Afterward, he started with a residency at the Department of Cardiology, University Hospital RWTH Aachen (Germany). In parallel he focused in the field of EPC research and RBC function always with a special refer to nitric oxide.

24 xxiv About the Authors Prof. Laura Poole-Warren, PhD She is a professor of biomedical engineering at the University of New South Wales (UNSW). She is a leader in the biomaterials and tissue engineering field with specific emphasis on development of bioactive polymers and understanding cell and tissue interactions with these materials. She is the International Liaison Delegate for the IUS-BSE representing Australia and New Zealand and is a council member of the Asian Biomaterials Federation. Olivier Preynat-Seauve, PhD He is a pharmacist, initially involved in the study of anti-tumor immunity. Actually, he is a biologist interested in the field of embryonic stem cell differentiation. He is working on neuronal differentiation of stem cells focusing on three main application: tissue engineering, cell therapy of neurodegenerative disorders, and understanding of early events of neural differentiation. Jan Pruszak, PhD He obtained his medical degree from Hannover Medical School (MHH) in Germany in He then pursued postdoctoral training at Harvard Medical School, Boston, MA, USA, with Dr. Ole Isacson at the Center for Neuroregeneration Research. Since 2007, he holds an academic appointment as an instructor at Harvard Medical School and has been an affiliated faculty member of the Harvard Stem Cell Institute. His research interests include the regulation of growth and lineage specification of stem cells, in the context of developing novel therapeutic strategies for neurological disease.

25 About the Authors xxv Anne Roessger, PhD She studied biology and did her Ph.D. in bacterial resistance development at the University Hospital of Regensburg. In 2008 she started working as a lecturer at the Institute of Cellular and Molecular Anatomy, University of Regensburg, Regensburg, Germany. Prof. Dr. med. Angela Rösen-Wolff Professor She is head of the Clinical Research Unit of the Department of Pediatrics at the University Clinic Carl Gustav Carus in Dresden since Since then she has been investigating the underlying molecular mechanisms of human phagocyte defects and bone tissue engineering. She has collaborated in several research initiatives focusing on tissue engineering of bone and development of new biomimetic bone substitute materials. She developed an in vitro model of hydroxyapatite remodeling in a co-culture system of osteoblasts together with osteoclasts. She is author of more than 80 peer-reviewed international publications in the field of molecular virology, pediatric immunology, biotechnology, biomaterials, and tissue engineering. Silke Schwengberg, PhD After her studies in biology at the Ruhr University Bochum, she received her Ph.D. in cell biology and immunology at the University of Hannover. From 1999 to 2001 she worked as research scientist at the Janssen Research Foundation in Neuss (Germany) and Beerse (Belgium). In 2001 she joined the biotechnology startup Axiogenesis AG in Cologne, Germany, as senior scientist and is now head of the laboratory.

26 xxvi About the Authors Sarvpreet Singh student at the Medical University of Innsbruck, is involved in a clinical study to investigate recurrent or refractory high-grade glioma and anaplastic astrocytoma at the Neuro-Oncology Innsbruck since Since 2006 his research is focused on the irradiation sensitivity of mesenchymal stem cells and thus affiliated to the Department of Cranio-Maxillofacial and Oral Surgery at the Medical University of Innsbruck in collaborative conjunction with the Institute for Biomedical Aging Research of the Austrian Academy of Sciences. Prof. Hwal (Matthew) Suh, PhD He received D.D.S. and M.S.D. degrees in 1978 and 1984 from Yonsei University, Seoul, Korea. He attended at the Columbia Institute of Materials Science and Technology in New York, USA, from 1985 till 1987 and moved to Japan to receive Ph.D. in 1992 from Osaka University. As his major is nanobiomaterials for the regenerative medicine, he had served as the director of National Brain Korea 21 Project Team of Nanobiomaterials for the Cell-Based Implants, the chair of Department of Medical Engineering in College of Medicine, and at present, he is chair professor of the Program of Nano Science and Technology in the Graduate School at Yonsei University. He is also the founder of the Korean Society for Biomaterials in Prof. Edda Tobiasch, PhD She is professor of Genetic Engineering and Cell Culture, has published several articles in international journals and in books. She holds several international patents and is referee member for various scientific committees at home and abroad. She has studied at the University of Kaiserlautern and made her Ph.D. at the German Cancer Research Center followed by postdoc positions at the Ruprecht-Karls University, Heidelberg, and the Forschungszentrum Karlsruhe. She was instructor at the Beth Israel Deaconess Medical Center in the Harvard Medical School, Boston, MA, USA.

27 About the Authors xxvii Prof. George Truskey, PhD is professor and chair of the Department of Biomedical Engineering at Duke University, Durham, NC, USA. His research interests are in cardiovascular tissue engineering and the effect of physical forces on cells. He is a fellow of the American Institute of Medical and Biological Engineering, the American Heart Association, and the Biomedical Engineering Society (BMES). He is currently president of BMES. Tsung-Neng Tsai, PhD He received clinical medical training and awarded the position of attending in Cardiovascular Division, Tri-service, General Hospital in Taiwan ( ). He won a national scholarship to allow his current studies toward a Ph.D. in stem cell research in King s College London, London. Prof. Gerald A. Urban, PhD He received the diploma (Dipl.-Ing.) for technical physics at Technical University Vienna. In 1985 he received the Ph.D. in electrical engineering at the TU Vienna. He was co-founder of the company OSC in Cleveland and Vienna. In 1994 he received the Venia Legendi for Sensor Technology. In 1997 he became full professor of sensors at the Institute for Microsystem Technology at the Albert Ludwig University Freiburg/Germany. He joined the Freiburg Institute of Advanced Studies (FRIAS) in His main interest focuses on research and development of microsensor applications including microthermistors, flow sensors and chemosensors and biosensors including oxygen. Recently nano- and microsystem technology is the main field of interest including the development of microarrays for proteomics and cell-based microassays.

28 xxviii About the Authors Jean Villard, MD, PhD He is head of the Immunology and Transplant Unit and chargé de cours at the University Geneva Hospital and medical school. His main research of interests are the immune response after tissue and solid organ transplantation, with a special focus on the natural killer cells immunity at the genetic and functional level. Prof. Yen Wei, PhD He received B.S. and M.S. in chemistry at Peking University in China in 1979 and 1981, respectively. He then earned his Ph.D. from the City University of New York in After postdoctoral work at MIT, he joined Drexel University, Philadelphia, PA, USA, in 1987, where he is currently the Herman B. Wagner Professor of Chemistry and Director of the Center for Advanced Polymers and Materials Chemistry. His awards include the ACS Philadelphia Section Award, Drexel Research Achievement Award, and DuPont Young Faculty Award. Recently, he was honored with an endowed Chang Jiang Lecture-Chair Professorship at Shanghai Jiao Tong University in China, a Nanochemistry Chair Professorship at Chung-Yuan Christian University, and an Honorary Chair Professorship at National I-Lan University in Taiwan. Robin Wesselschmidt She is president, Primogenix, Inc., a company specializing in the derivation, characterization, and distribution of mouse embryonic stem cells. She has been actively working with and deriving mouse embryonic stem cells since She has derived and commercialized several widely used lines, including the RW4 and GSI-1 lines. She is focused on developing, streamlining, and translating research techniques into robust operations that can be utilized in core laboratories or developed into viable business operations. Since 2004, she has been a co-director and instructor for two of the seven NIH-sponsored human embryonic stem cell training courses held biannually in Southern California. She has written and co-edited papers and book chapters, as well as a laboratory manual in the area of pluripotent stem cell technologies.

29 About the Authors xxix Andreas Wilmen, PhD He received his Ph.D. in biology in He received his postdoc at the Clinical Research Group for Gastrointestinal Endocrinology, University of Marburg, Germany. Employment followed at the Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, USA. He is presently a senior scientist at the Institute for Target Discovery, Bayer Schering Pharma AG, Wuppertal, Germany. Prof. Qingbo Xu, MD PhD He is professor and BHF John Parker Chair of Cardiovascular Sciences, Cardiovascular Division at King s College London, and studied in China, USA, and Austria before moving to London. He received several awards nationally and internationally. His research interests focus on stem cells and vascular diseases. Prof. Masayuki Yamato, PhD He is a professor of the Institute of Advanced Biomedical Engineering and Science at Tokyo Women s Medical University. He was originally trained with a background in cell biology and biochemistry, but over the past decade, his research interests have been focused on the regeneration of various tissues and organs, such as the cornea, using cell sheets, instead of traditional tissue engineering approaches using cells seeded into biodegradable scaffolds. In particular, his work with both corneal and oral mucosal epithelial cell sheets has already been applied to human patients suffering from ocular surface dysfunctions. He is currently engaged in research collaborations with physicians and surgeons from various medical departments, with the aim of taking regenerative medicine using cell sheets from the level of basic laboratory science to clinical applications.

30

31 Contents Part I Instead of an Introduction The Emperor s New Legs The Emperor s New Body: Seeking for a Blueprint of Limb Regeneration in Humans... 3 Ilya Digel and Aysegül Temiz Artmann Part II Basics and Basic Research Engineering the Stem Cell Niche and the Differentiative Microand Macroenvironment: Technologies and Tools for Applying Biochemical, Physical and Structural Stimuli and Their Effects on Stem Cells Paolo Di Nardo, Marilena Minieri, and Arti Ahluwalia Differentiation Potential of Adult Human Mesenchymal Stem Cells.. 61 Edda Tobiasch The Potential of Selectively Cultured Adult Stem Cells Re-implanted in Tissues Isgard S. Hueck, Martin Haas, Rita Finones, Jane Frimodig, and David A. Gough Enhanced Cardiac Differentiation of Mouse Embryonic Stem Cells by Electrical Stimulation Paul R. Bidez III, J. Yasha Kresh, Yen Wei, and Peter I. Lelkes The Therapeutic Potential of ES-Derived Haematopoietic Cells Sabrina Gordon-Keylock and Lesley Forrester Genetic Modification of Human Embryonic and Induced Pluripotent Stem Cells: Viral and Non-viral Approaches Nicole M. Kane, Chris Denning, and Andrew H. Baker The Immune Barriers of Cell Therapy with Allogenic Stem Cells of Embryonic Origin Olivier Preynat-Seauve, Karl-Heinz Krause, and Jean Villard xxxi

32 xxxii Contents Reponses of Mesenchymal Stem Cells to Varying Oxygen Availability In Vitro and In Vivo Frank R. Kloss, Sarvpreet Singh, and Günter Lepperdinger Endothelial Progenitor Cells and Nitric Oxide: Matching Partners in Biomedicine Stefanie Keymel, Burcin Özüyaman, Marijke Grau, Malte Kelm, and Petra Kleinbongard Skeletal Stem Cells and Controlled Nanotopography Matthew J. Dalby and Richard O.C. Oreffo Part III Clinical Applications Cells and Vascular Tissue Engineering John Paul Kirton, Tsung-Neng Tsai, and Qingbo Xu Endothelial Progenitor Cells for Vascular Repair Melissa A. Brown, Cindy S. Cheng, and George A. Truskey Regenerating Tubules for Kidney Repair W.W. Minuth, L. Denk, and A. Roessger Stem Cells in Tissue Engineering and Cell Therapies of Urological Defects Christoph Becker, Katrin Montzka, and Gerhard Jakse Bio-synthetic Encapsulation Systems for Organ Engineering: Focus on Diabetes Rylie A. Green, Penny J. Martens, Robert Nordon, and Laura A. Poole-Warren Stem Cell Engineering for Regeneration of Bone Tissue Michael Gelinsky, Anja Lode, Anne Bernhardt, and Angela Rösen-Wolff Part IV Techniques and Applications Building, Preserving, and Applying Extracellular Culture Integrity Using New Cell Culture Methods and Surfaces Thomas Brevig, Robin Wesselschmidt, and Masayuki Yamato Fabrication of Modified Extracellular Matrix for the Bone Marrow-Derived Mesenchymal Stem Cell Therapeutics Hwal (Matthew) Suh Neural Stem Cells: From Cell Fate and Metabolic Monitoring Toward Clinical Applications Jan Pruszak, Máté Döbrössy, Jochen Kieninger, Kuppusamy Aravindalochanan, Gerald A. Urban, and Guido Nikkhah

33 Contents xxxiii Adult Stem Cells in Drug Discovery Stefan Golz, Andreas Geerts, and Andreas Wilmen Embryonic Stem Cells as a Tool for Drug Screening and Toxicity Testing 473 Bernd Denecke and Silke Schwengberg Embryonic Stem Cells: A Biological Tool to Translate the Mechanisms of Heart Development Omonigho A. Aisagbonhi and Antonis K. Hatzopoulos Index

34

35 Contributors Arti Ahluwalia Interdepartmental Research Centre E. Piaggio, University of Pisa, Pisa, Italy, Omonigho A. Aisagbonhi Division of Cardiovascular Medicine, Department of Cell and Developmental Biology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Kuppusamy Aravindalochanan Laboratory for Sensors, Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany Aysegül Temiz Artmann Laboratory of Medical and Molecular Biology, Institute of Bioengineering, Aachen University of Applied Sciences, Jülich, Germany Andrew H. Baker Faculty of Medicine, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK, Christoph Becker Department of Urology, University Hospital and Medical Faculty, RWTH Aachen University, Aachen, Germany, Anne Bernhardt The Max Bergmann Center of Biomaterials, Institute of Materials Science, Technische Universität Dresden, Dresden, Germany Paul R. Bidez, III School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, USA; Merck Research Laboratories, Merck & Co., North Wales, PA, USA, Thomas Brevig Research and Development, Thermo Fisher Scientific, Roskilde, Denmark, Melissa A. Brown Department of Biomedical Engineering, Duke University, Durham, NC, USA Cindy S. Cheng Department of Biomedical Engineering, Duke University, Durham, NC, USA xxxv

36 xxxvi Contributors Matthew J. Dalby Centre for Cell Engineering, Joseph Black Building, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK Bernd Denecke IZKF BIOMAT., RWTH Aachen, Germany, Lucia. Denk Department of Molecular and Cellular Anatomy, University of Regensburg, Regensburg, Germany Chris Denning Wolfson Centre for Stem Cells, Tissue Engineering & Modelling (STEM), Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK Paolo Di Nardo Laboratory of Molecular and Cellular Cardiology, Department of Internal Medicine, University of Rome Tor Vergata and National Institute for Cardiovascular Research (INRC), Bologna, Italy Ilya Digel Laboratory of Cell- and Microbiology, Institute of Bioengineering, Aachen University of Applied Sciences, Jülich, Germany, Máté Döbrössy Laboratory of Molecular Neurosurgery, Department of Stereotactic and Functional Neurosurgery, Albert Ludwigs University Freiburg, Freiburg, Germany Rita Finones Department of Mechanical and Aerospace Engineering, Division of Biology and Material Science, University of California San Diego, La Jolla, CA, USA Lesley Forrester Centre for Regenerative Medicine, University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4YJ Jane Frimodig Department of Bioengineering, University of California San Diego, La Jolla, CA, USA Andreas Geerts Bayer Schering Pharma AG, Target Discovery, Wuppertal, Germany Michael Gelinsky The Max Bergmann Center of Biomaterials, Institute for Materials Science, Technische Universität Dresden, Dresden, Germany; DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany, Stefan Golz Bayer Schering Pharma AG, Target Discovery, Wuppertal, Germany, Sabrina Gordon-Keylock Centre for Regenerative Medicine, University of Edinburg, Rodger Land Building, Kings Buildings, West main road, Edinburg E49 3JQ