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Handbook of Stem Cells, Two-Volume Set: Volume 1-Embryonic Stem Cells; Volume 2-Adult & Fetal Stem Cells PDF

1633 Pages·2004·128.35 MB·English
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Preview Handbook of Stem Cells, Two-Volume Set: Volume 1-Embryonic Stem Cells; Volume 2-Adult & Fetal Stem Cells

P436643-V1-FM 31/07/04 4:09 PM Page ix Contributors Numbers in parentheses indicate the chapter to which the author contributed. Russell C. Addis (43) Daniel Becker, MD (69) Johns Hopkins University School of Medicine, Institute for Department of Neurology, Vanderbilt University Medical Cellular Engineering, Baltimore, MD Center, Nashville, TN Bruce Alberts, PhD (Foreword) Nissim Benvenisty, MD, PhD (53, 66) President, National Academy of Sciences, Washington, DC Professor of Genetics, Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Michal Amit, PhD (40) Jerusalem, Israel Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel Mickie Bhatia, PhD (38, 50) Director and Scientist, Stem Cell Biology and Regenerative Peter W. Andrews (9, 56) Medicine, Robarts Research Institute, The Krembil Centre Arthur Jackson Professor of Biomedical Science, for Stem Cell Biology, Associate Professor, Faculty of Department of Biomedical Science, The University of Medicine, University of Western Ontario, London, Ontario, Sheffield, Western Bank, United Kingdom Canada Hitomi Aoki (20) C. Clare Blackburn, PhD (37) Department of Tissue and Organ Development, Regeneration Leukaemia Research Fund Senior Fellow, Institute for Stem and Advanced Medical Science, Gifu University Graduate Cell Research, University of Edinburgh, Edinburgh, United School of Medicine, Japan Kingdom Makoto Asashima, PhD (46) Michele Boiani, PhD (64) Dean and Professor, Department of Life Sciences, Department of Animal Biology, University of Pennsylvania University of Tokyo, Meguro-ku, Tokyo, Japan (New Bolton Center), Kennett Square, PA Joyce Axelman (43) Susan Bonner-Weir, PhD (71) Johns Hopkins University School of Medicine, Institute for Associate Professor/Senior Investigator, Diabetes Center, Cellular Engineering, Baltimore, MD Harvard University, Boston, MA ix P436643-V1-FM 31/07/04 4:09 PM Page x Contributors Josephine Bowles, PhD (33) Jérôme Collignon, PhD (11) Institute for Molecular Bioscience, The University of Department of Developmental Biology, Institut Jacques Queensland, Brisbane, Queensland, Australia Monod, Paris, France Richard L. Boyd, PhD (67) Paul Collodi, PhD (47) Associate Professor, Department of Pathology and Professor, Department of Animal Sciences, Purdue Immunology, Monash University, Melbourne, Victoria, University, West Lafayette, IN Australia Chad Cowan, PhD (Foreward) Marianne Bronner-Fraser, PhD (19) Department of Molecular and Cellular Biology, Harvard California Institute of Technology, Division of Biology, University, Cambridge, MA Beckman Institute, Pasadena, CA George Q. Daley, MD, PhD (25) Eric W. Brunskill, PhD (58) Division of Hematology/Oncology, Children's Hospital, Professor, Division of Cardiology, University of Cincinnati Boston, MA College of Medicine, Cincinnati, OH Christian Dani, PhD (31) Scott Bultman, PhD (6) Director of Research INSERM, Centre de Biochimie CNRS Department of Genetics, University of North Carolina, UMR6543, Institute of Signaling, Developmental Biology Chapel Hill, NC and Cancer, University of Nice-Sophia Antipolis, Nice, France Frederick Charles Campbell, MD (35) Professor, Department of Surgery, Cancer Centre, Queen's Joshua D. Dowell, MD, PhD (70) University of Belfast, Belfast, Antrim, Northern Ireland Department of Medicine, Indiana University School of Medicine, Indianapolis, IN Anne Camus, PhD (11) Department of Developmental Biology, Institut Jacques Jonathan S. Draper, PhD (56) Monod, Paris, France Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom Melissa K. Carpenter, PhD (38, 52) Stem Cell Biology and Regenerative Medicine, Robarts Gregory R. Dressler, PhD (32) Research Institute, Associate Professor, Faculty of Medicine, Associate Professor, Department of Pathology, University of University of Western Ontario, London, Ontario, Canada Michigan, Ann Arbor, MI Fatima Cavaleri (3) Micha Drukker (66) Max Planck Institute for Molecular Biomedicine, Department of Genetics, Silberman Institute of Life Department of Cell and Developmental Biology, Münster, Sciences, The Hebrew University, Jerusalem, Israel Germany Gabriela Durcova-Hills, PhD (42) Constance Cepko, PhD (22) Professor, The Wellcome Trust/Cancer Research UK Gurdon Professor, Department of Genetics, Investigator, Howard Institute, University of Cambridge, Cambridge, Hughes Medical Institute, Harvard Medical School, Boston, Cambridgeshire, United Kingdom MA Robert G. Edwards (1) Yijing Chen, PhD (60) Chief Editor, Reproductive BioMedicine Online, Duck End Department of Genetics, University of North Carolina, Farm, Dry Drayton, Cambridge, United Kingdom Chapel Hill, NC Rebecca S. Eisenberg, JD (79) Susana M. Chuva de Sousa Lopes, PhD (12) Robert and Barbara Luciano Professor of Law, University of Professor, Hubrecht Laboratory, University of Utrecht, Michigan Law School, Ann Arbor, MI Utrecht, The Netherlands Ravindhra Elluru (36) Gregory O. Clark, MD (43) Divisions of Neonatology and Pulmonary Biology, Johns Hopkins University School of Medicine, Institute for Cincinnati Children’s Hospital Medical Center, Cellular Engineering, Baltimore, MD Cincinnati, OH x P436643-V1-FM 31/07/04 4:09 PM Page xi Contributors Sir Martin Evans, PhD (39) Sharon Gerecht-Nir, PhD (30) Director and Professor, Cardiff School of Biosciences, Bruce Rappaport Faculty of Medicine, Technion-Israel Cardiff University, Wales, United Kingdom Institute of Technology, Haifa, Israel Lianchun Fan, PhD (47) Jason W. Gill, PhD (67) Research Associate, Department of Animal Sciences, Purdue Department of Pathology and Immunology, Monash University, West Lafayette, IN University, Melbourne, Victoria, Australia Margaret A. Farley, PhD (76) Rodolfo Gonzalez, MS (68) Gilbert Stark Professor of Christian Ethics, Divinity School Joint Program in Molecular Pathology, The Burnham and Department of Religious Studies, Yale University, Institute and the University of California, San Diego, La New Haven, CT Jolla, CA Donna M. Fekete, PhD (22) Daniel H.D. Gray, PhD (67) Department of Neurobiology, Harvard Medical School, Department of Pathology and Immunology, Monash Boston, MA University, Melbourne, Victoria, Australia Loren J. Field, PhD (70) Ronald M. Green, PhD (75) Professor of Medicine, Department of Medicine, Indiana Director, Ethics Institute, Eunice and Julian Cohen Professor University School of Medicine, Indianapolis, IN for the Study of Ethics and Human Values, Chair, Department of Religion, Dartmouth College, Hanover, NH Donald W. Fink Jr., PhD (77) Biologist, Division of Cell and Gene Therapy, Center for Michal Gropp, PhD (55) Biologics Evaluation and Research/US Food and Drug The Hadassah Embryonic Stem Cell Research Center, The Administration, Rockville, MD Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel Lesley M. Forrester, PhD (34) John Hughes Bennett Laboratories, Department of Alexandra Haagensen (71) Oncology, University of Edinburgh, Western General Section on Islet Transplantation and Cell Biology, Joslin Hospital, Edinburgh, United Kingdom Diabetes Center, Harvard Medical School, Boston, MA Margaret T. Fuller, PhD (14) F. Kent Hamra, PhD (15) Professor, Departments of Developmental Biology and Department of Pharmacology and The Cecil H. and Ida Genetics, Stanford University School of Medicine, Green Center for Reproductive Biology Sciences, The Stanford, CA University of Texas Southwestern Medical Center at Dallas, Dallas, TX Miho Furue, DDS, PhD (46) Department of Biochemistry and Molecular Biology, Richard P. Harvey, PhD (28) Kanagawa Dental College, Yokosuka, Kanagawa, Japan Sir Peter Finley Professor of Cardiac Research, Head, Developmental Biology Program, Victor Chang Cardiac David L. Garbers, PhD (15) Research Institute, Darlinghurst, New South Wales, Australia Director of The Cecil H. and Ida Green Center for Reproductive Biology Sciences, Investigator, Howard Susan M. Hawes, PhD (48) Hughes Medical Institute, Professor of Pharmacology, The Research Fellow, Institute for Reproduction and University of Texas Southwestern Medical Center at Dallas, Development, Monash University, Melbourne, Victoria, Dallas, TX Australia Richard L. Gardner (2) Shin-Ichi Hayashi, MD, PhD (27) E P Abraham Research Professor of the Royal Society in the Professor, Division of Immunology, Department of University of Oxford, Departement of Zoology, University of Molecular and Cellular Biology, School of Life Science, Oxford, Oxford, United Kingdom Faculty of Medicine, Tottori University, Tottori, Japan John D. Gearhart, PhD (43) Anne L. Hazlehurst (78) Johns Hopkins University School of Medicine, Institute for Center for Biomedical Engineering, Brown University, Cellular Engineering, Baltimore, MD Providence, RI xi P436643-V1-FM 31/07/04 4:09 PM Page xii Contributors Hiroaki Hemmi, PhD (27) Pritinder Kaur, PhD (72) Ralph Steinman Laboratory, Cellular Physiology and Head, Epithelial Stem Cell Biology Laboratory, Stem Cell Immunology, Rockefeller University, New York, NY Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Hiroshi Hisatsune (29) Department of Molecular Genetics, Graduate School of Robert G. Kelly (28) Medicine, Kyoto University, Kyoto, Japan Department of Genetics and Development, Columbia University, New York, NY James Huettner, PhD (69) Center for the Study of Nervous System Injury and the Kathleen C. Kent (43) Restorative Treatment and Research Program, Department of Johns Hopkins University School of Medicine, Institute for Cell Biology and Physiology, Washington University School Cellular Engineering, Baltimore, MD of Medicine, St. Louis, MO Candace L. Kerr, PhD (43) Bradley Huntsman, BS (58) Johns Hopkins University School of Medicine, Institute for Division of Developmental Biology, Cincinnati Children’s Cellular Engineering, Baltimore, MD Hospital Medical Center, University of Cincinnati, Cincinnati, OH Ali Khademhosseini, MASc (73) Division of Biological Engineering, Massachusetts Institute Catherine Iéhlé, PhD (31) of Technology, Cambridge, MA Senior Scientist, Unité de Virologie, Institut Pasteur de Madagascar, Antananarivo, Madagascar Hanita Khaner, PhD (49) Research Associate, The Hadassah Embryonic Stem Cell Jamie Imitola, MD (68) Research Center, Goldyne Savad Institute of Gene Therapy, Department of Neurology, Brigham and Women's Hospital, Hadassah University Hospital, Jerusalem, Israel Boston, MA Joseph Itskovitz-Eldor, MD, DSc (30, 40) Chris Kintner, PhD (18) Professor and Director, Department of Obstetrics and Professor, Molecular Neurobiology Laboratory, The Salk Gynecology, Rambam Medical Center and Bruce Rappaport Institute for Biological Studies, La Jolla, CA Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Irina Klimanskaya, PhD (41) Senior Scientist, Advanced Cell Technology, Worcester, MA Rudolf Jaenisch, MD (10) Professor of Biology, Whitehead Institute for Biomedical Nobuyuki Kondoh (29) Research, Department of Biology, Massachusetts Institute of Satomi Nishikawa, Riken Center for Developmental Technology, Cambridge, MA Biology, Kobe, Japan Penny A. Johnson, PhD (9) Peter Koopman, PhD (33) Senior Research Scientist, Intercytex Ltd., Manchester, Professor of Developmental Biology, Institute for Molecular United Kingdom Bioscience, The University of Queensland, Brisbane, Queensland, Australia D. Leanne Jones, PhD (14) Department of Developmental Biology, Naoko Koyano-Nakagawa, PhD (18) Stanford University School of Medicine, Assistant Professor, Department of Neuroscience, University Stanford, CA of Minnesota, Minneapolis, MN Elizabeth A. Jones, MA, MB, BChir, MRCP, PhD (34) Jennifer N. Kraszewski (43) Institute of Human Genetics, University of Newcastle upon Johns Hopkins University School of Medicine, Institute for Tyne, Newcastle upon Tyne, United Kingdom Cellular Engineering, Baltimore, MD Gerard Karsenty, MD, PhD (26) Professor of Molecular and Human Genetics, Baylor College Robb Krumlauf, PhD (19) of Medicine, Houston, TX Scientific Director, Stowers Institute for Medical Research, Kansas City, MO Gil Katz, PhD (66) The Lautenberg Center for General and Tumor Immunology, Tilo Kunath, PhD (17, 45) Hadassah Medical School, The Hebrew University, Institute for Stem Cell Research, University of Edinburgh, Jerusalem, Israel Edinburgh, United Kingdom xii P436643-V1-FM 1/7/05 9:49 AM Page xiii Contributors Takahiro Kunisada, PhD (20) Klaus I. Matthaei, PhD (59) Professor, Department of Tissue and Organ Development, Senior Fellow and Head, Gene Targeting Laboratory, The Regeneration and Advanced Medical Science, Gifu John Curtin School of Medical Research, The Australian University Graduate School of Medicine, Gifu, Japan National University, Canberra, ACT, Australia Robert Langer, ScD (73) Yoav Mayshar, (53) Professor, Department of Chemical Engineering, Departmentof Genetics, The Silberman Institute for Life Massachusetts Institute of Technology, Cambridge, MA Sciences, The Hebrew University, Jerusalem, Israel Robert Lanza, MD (Preface) John W. McDonald, MD, PhD (69) Vice President, Medical and Scientific Development, Associate Professor of Neurology, Neurological Surgery and Advanced Cell Technology, Adjunct Professor of Surgical Anatomy and Neurobiology, Director of the Spinal Cord Sciences, Institute of Regenerative Medicine, Wake Forest Injury Program, Restorative Treatment and Research Center, University School of Medicine, Winston-Salem, NC Washington University School of Medicine, St. Louis, MO Jean Pyo Lee, PhD (68) Dame Anne McLaren, PhD (16, 42) Department of Neurology, Beth Israel Deaconess Medical Professor, The Wellcome Trust/Cancer Research UK Gurdon Center, Boston, MA Institute, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom Shulamit Levenberg, PhD (73) Research Associate, Langer Laboratory, Department of Jill McMahon, MSc (41) Chemical Engineering, Massachusetts Institute of Molecular and Cellular Biology Department, Harvard Technology, Cambridge, MA University, Cambridge, MA S. Robert Levine, MD (80) Alexander Meissner, Dipl Ing (10) Board of Chancellors, Juvenile Diabetes Research Whitehead Institute for Biomedical Research, Massachusetts Foundation International, New York, NY Institute of Technology, Cambridge, MA Haifan Lin, PhD (13) Harald von Melchner, MD, PhD (61) Associate Professor, Department of Cell Biology, Duke Professor of Cell Biology and Molecular Genetics, University Medical School, Durham, NC Department of Molecular Hematology, University of Frankfurt Medical School, Frankfurt am Main, Germany John W. Littlefield, MD (43) Johns Hopkins University School of Medicine, Institute for Douglas A. Melton, PhD (Foreword) Cellular Engineering, Baltimore, MD Thomas Dudley Cabot Professor in the Natural Sciences, Department of Molecular and Cellular Biology, Harvard Michael J. Lysaght, PhD (78) University, Investigator, Howard Hughes Medical Institute, Professor and Director, Center for Biomedical Engineering, Cambridge, MA Brown University, Providence, RI Fiona A. Mack (7) Nathan Montgomery (6) Cell Growth and Cancer Graduate Group, University of Department of Genetics, University of North Carolina, Pennsylvania, Philadelphia, PA Chapel Hill, NC Terry Magnuson, PhD (6, 60) Mary Tyler Moore (80) Professor, Department of Genetics, University of North International Chairman, Juvenile Diabetes Research Carolina, Chapel Hill, NC Foundation, New York, NY Anna Malashicheva, PhD (5) Tsutomu Motohashi, PhD (20) Laboratory of Molecular Basis of Cell Differentiation, Department of Tissue and Organ Development, Regeneration Institute of Cytology, St. Petersburg, Russia and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan Ofer Mandelboim (66) The Lautenberg Center for General and Tumor Immunology, Franz-Josef Mueller, MD (68) Hadassah Medical School, The Hebrew University, Program in Developmental and Regenerative Cell Biology, Jerusalem, Israel The Burnham Institute, La Jolla, CA Nancy R. Manley, PhD (37) Christine Mummery, PhD (12) Associate Professor, Department of Genetics, University of Professor, Hubrecht Laboratory, University of Utrecht, Georgia, Athens, GA Utrecht, The Netherlands xiii P436643-V1-FM 31/07/04 4:09 PM Page xiv Contributors Satomi Nishikawa (29) Martin F. Pera, BA, PhD (48, 51) Riken Center for Developmental Biology Kobe, Japan Associate Professor, Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria, Shin-Ichi Nishikawa, MD, PhD (29) Australia Group Director, Stem Cell Research Group, Riken Center for Developmental Biology, Kobe, Japan Aitana Perea-Gomez, PhD (11) Department of Developmental Biology, Institut Jacques Andras Nagy, PhD (57) Monod, Paris, France Senior Scientist, Mount Sinai Hospital, Samuel Lunenfeld Research Institute, Professor, Department of Medical Anthony C.F. Perry, PhD (62) Genetics and Microbiology, University of Toronto, Toronto, Head of Laboratory, Laboratory of Mammalian Molecular Ontario, Canada Embryology, Riken Center for Developmental Biology, Hitoshi Niwa, MD, PhD (4) Kobe, Japan Laboratory for Pluripotent Cell Studies, Riken Center for Developmental Biology (CDB), Kobe, Hyogo, Japan James N. Petitte, PhD (44) Professor, Department of Poultry Science, College of Hiromi Okuyama (21) Agriculture and Life Sciences, North Carolina State Center for Cells and Gene Theraphy, Takara Bio Inc., Ostu, University, Raleigh, NC Shiga, Japan Blaine W. Phillips, PhD (31) Jitka Ourednik, PhD (68) Research Scientist, ES Cell International, Singapore Associate Professor, Department of Biomedical Sciences, Iowa State University, Ames, IA S. Steven Potter, PhD (58) Professor, Division of Developmental Biology, Cincinnati Vaclav Ourednik, PhD (68) Children’s Hospital Medical Center, University of Associate Professor, Department of Biomedical Sciences, Cincinnati, Cincinnati, OH Iowa State University, Ames, IA Arti K. Rai (79) Masahito Oyamada, MD, PhD (8) Professor of Law, Duke Law School, Duke University, Associate Professor, Department of Pathology and Cell Durham, NC Regulation, Kyoto Prefectural University of Medicine, Kyoto, Japan Christopher Reeve (81) Chairman, Christopher Reeve Paralysis Foundation, Yumiko Oyamada, MD, PhD (8) Springfield, NJ Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Kyoto, Japan Benjamin Reubinoff, MD, PhD (49, 55) Virginia E. Papaioannou, PhD (24) Associate Professor in Obstetrics and Gynecology, Director, Professor of Genetics and Development, Department of The Hadassah Embryonic Stem Cell Research Center, The Genetics and Development, College of Physicians and Goldyne Savad Institute of Gene Therapy, Department of Surgeons of Columbia University, New York, NY Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem, Israel Kook I. Park, MD (68) Professor, Department of Pediatrics and Pharmacology, Janet Rossant, PhD (17, 45, Foreword) Yonsei University College of Medicine, Seoul, Korea Senior Investigator, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada Ethan S. Patterson (43) Johns Hopkins University School of Medicine, Institute for Michael Rubart, MD (70) Cellular Engineering, Baltimore, MD Department of Medicine, Indiana University School of Medicine, Indianapolis, IN Larry T. Patterson, MD (58) Professor, Division of Nephrology and Hypertension, Pierre Savatier, PhD (5) Cincinnati Children’s Hospital Medical Center, University of Director of Research, U371 “Cerveau et Vision”, Institut Cincinnati, Cincinnati, OH National de la Santé et de la Recherche Médicale, Bron, France Alice Pébay, PhD (51) Hans Schöler (3, 64) Monash Institute of Reproduction and Development, Max Planck Institute for Molecular Biomedicine, Department Monash University, Clayton, Victoria, Australia of Cell and Developmental Biology, Münster, Germany xiv P436643-V1-FM 31/07/04 4:09 PM Page xv Contributors Cordula Schulz, PhD (14) James A. Thomson, VMD, PhD, Dipl. ACVP (54) Research Investigator, Cold Spring Harbor Laboratory, Cold John D. MacArthur Professor, Department of Anatomy, Spring Harbor, NY University of Wisconsin–Madison Medical School, The Wisconsin National Primate Research Center, Madison, WI Nikolaus Schultz, PhD (15) The Cecil H. and Ida Green Center for Reproductive David Tosh, PhD (34) Biology Sciences, The University of Texas Southwestern Biology and Biochemistry, University of Bath, Bath, United Medical Center at Dallas, Dallas, TX, Freie Universität Kingdom Berlin, Institut für Biochemie, Thielallee 63, Berlin, Germany Paul Trainor, PhD (19) Stowers Institute for Medical Research, Kansas City, MO Michael J. Shamblott, PhD (43) Johns Hopkins University School of Medicine, Institute for Alan O. Trounson, PhD (67) Cellular Engineering, Baltimore, MD Professor of Stem Cell Sciences, Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Victoria, Australia Richard L. Sidman, MD (68) Bullard Professor of Neuropathology, Emeritus, Harvard Motokazu Tsuneto (27) Medical School, Boston, MA Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Tottori University, M. Celeste Simon, PhD (7) Tottori, Japan Associate Investigator, Howard Hughes Medical Institute, Associate Professor, Abramson Family Cancer Research Mark Tummers, MSc (23) Institute and Department of Cell and Developmental Developmental Biology Programme, Institute of Biology, University of Pennsylvania School of Medicine, Biotechnology, University of Helsinki, Finland Philadelphia, PA Edward Upjohn, MD (72) Evan Y. Snyder, MD, PhD (68) Department of Dermatology, Royal Children’s Hospital, Professor and Director, Program in Developmental and Melbourne, Victoria, Australia Regenerative Cell Biology, The Burnham Institute, La Jolla, CA George Varigos, MB, BS, PhD, FACD (72) Department of Dermatology, Royal Melbourne and A. Francis Stewart, PhD (61) Childrens’Hospitals, Parkville, Victoria, Australia Professor, Department of Genomics, BioInnovationZentrum, Dresden University of Technology, Dresden, Germany Cécile Vernochet, PhD (31) Centre de Biochimie CNRS UMR6543, Institute of Lorenz Studer, MD (21, 62) Signaling, Developmental Biology and Cancer, University of Developmental Biology and Neurosurgery, Memorial Sloan Nice-Sophia Antipolis, Nice, France Kettering Cancer Center, New York, NY Jay L. Vivian, PhD (60) Azim Surani, PhD (65) Department of Genetics, University of North Carolina, Wellcome Trust/Cancer Research UK Gurdon Institute, Chapel Hill, NC University of Cambridge, Cambridge, United Kingdom Zhongde Wang, PhD (10) Tetsuro Takamatsu, MD, PhD (8) Whitehead Institute for Biomedical Research, Massachusetts Professor, Department of Pathology and Cell Regulation, Institute of Technology, Cambridge, MA Kyoto Prefectural University of Medicine, Kyoto, Japan Gordon C. Weir, MD (71) Yang D. Teng, MD, PhD (68) Professor of Medicine, Harvard Medical School, Head, Assistant Professor, Department of Neurosurgery, Harvard Section on Islet Transplantation and Cell Biology, Diabetes Medical School/Children’s Hospital, Boston/Brigham and Research and Wellness Foundation, Chair, Joslin Diabetes Women’s Hospital, Boston, and SCI Laboratory, VA Boston Center, Boston, MA Healthcare System, Boston, MA Susan E. Wert (36) Irma Thesleff, DDS (23) Divisions of Neonatology and Pulmonary Biology, Professor, Research Director, Institute of Biotechnology, Cincinnati Children’s Hospital Medical Center, Cincinnati, University of Helsinki, Helsinki, Finland OH xv P436643-V1-FM 31/07/04 4:09 PM Page xvi Contributors Jeffrey A. Whitsett, MD (36) Yukiko M. Yamashita, PhD (14) Professor of Pediatrics, Chief, Section of Neonatology, Department of Developmental Biology, Stanford University Pulmonary, and Perinatal Biology, Cincinnati Children's School of Medicine, Stanford, CA Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH Hidetoshi Yamazaki, DDS, PhD (27) Associate Professor, Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and J. David Wininger, PhD (63) Regenerative Therapeutics, Institute of Regenerative Wake Forest University Baptist Medical Center, Program for Medicine and Biofunction, Tottori University Graduate Assisted Reproduction, Department of Obstetrics and School of Medical Science, Division of Immunology, Gynecology, Winston-Salem, NC Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Zhuoru Wu, PhD (15) Tottori, Japan Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX Laurie Zoloth, PhD (74) Professor of Medical Humanities and of Religion, Medical Chunhui Xu, PhD (52) Humanities and Bioethics, Feinberg School of Medicine, Senior Scientist, Geron Corporation, Menlo Park, CA Northwestern University, Chicago, IL Toshiyuki Yamane, PhD (20, 27) Thomas P. Zwaka, MD (54) Irving Weissman Laboratory, Department of Pathology, The Wisconsin National Primate Research Center, Stanford University School of Medicine, Stanford, CA Madison, WI Jun Yamashita (29) Robert Zweigerdt, PhD (70) Department of Molecular Genetics, Graduate School of Department of Medicine, Heinrich Heine University, Medicine, Kyoto University, Kyoto, Japan Duesseldorf, Germany xvi P436643-V1-FM 31/07/04 4:09 PM Page xvii Preface New discoveries in the field of stem cells increasingly dominate early development, ectoderm, mesoderm, endoderm, methods the news and scientific literature. Wave upon wave of papers (such as detailed descriptions of how to derive and maintain has led to an avalanche of new knowledge and research tools animal and human embryonic stem cells), application of stem that may soon lead to new therapies for cancer, heart disease, cells to specific human diseases, regulation and ethics, and diabetes, and a wide variety of other diseases that afflict patient perspectives from Mary Tyler Moore (diabetes) and humanity. The Handbook of Stem Cellsintegrates this exciting Christopher Reeve (spinal cord injury). The result is a com- area of biology, combining in two volumes the prerequisites prehensive two-volume reference that will be useful for stu- for a general understanding of adult and embryonic stem cells; dents and experts alike. It represents the combined effort of the tools, methods, and experimental protocols needed to study 12 editors and more than 300 scholars and scientists whose and characterize stem cells and progenitor populations; as well as pioneering work has defined our understanding of stem cells. a presentation by the world’s experts of what is currently known about each specific organ system. No topic in the field of stem Robert Lanza, MD cells is left uncovered, including basic biology/mechanisms, Boston, Massachusetts xvii P436643-V1-FM 31/07/04 4:09 PM Page xix Foreword What can usefully be said about stem cells in a foreword to a through the efforts of a large number of independent scientists collection of definitive articles by the world’s experts, inasmuch and engineers. Each piece of knowledge, often seemingly as this volume already covers every conceivable aspect of the useless on its own, was combined in unexpected ways with subject? In response to this question, I shall attempt to place the other knowledge to produce a final result whose power seems work described here in the broader context of science—and of almost magical. modern cell and developmental biology specifically. The great enterprise of science, sparked simply by human My view of the science in this book comes from the per- curiosity about how the world works—for example, an spective of someone who spent 30 years in universities prob- attempt to account for the motions of the planets in the ing the molecular details of basic cell processes. Over this night sky—has transformed our world. And because new time, our understanding of cells increased at a rate that star- knowledge builds on old knowledge, the pace continually tled even those most closely involved in the wave upon wave accelerates as the amount of old knowledge increases. Thus, of new discoveries. This increase in knowledge was catalytic: we should expect the inventions that benefit humans in this As our understanding of cells advanced, it allowed new new century to be even more dramatic than those of the last research tools to be developed that directly sped further century. But we can be equally sure of the futility of attempting advances in understanding, which in turn led to new tools, and to predict what they will be in advance. so on. Consider, for example, the DNA chip technology What does all this have to do with stem cells? Personally, described in Chapter 58 of Volume one and Chapter three of I become uncomfortable whenever I hear claims that describe Volume two, which allows an investigator to examine the the precise benefits to be derived from this research—especially expression of tens of thousands of genes simultaneously. when they are associated with a timeline. Nevertheless, the Because hundreds of small steps were needed to move from the history of science makes it certain that the knowledge derived striking initial discovery of DNA hybridization in 19611to this from research on stem cells will eventually lead to enormous new technology, its development was unpredictable in advance. benefits for human health, even if they are unpredictable. It is the same for the advance of science itself, as empha- Eventually, we will be able to use our profound understanding sized repeatedly in the “Beyond Discovery” series of brief of biology to grow new organs that can be safely transplanted articles from the National Academy of Sciences.2Designed to into human patients, and the work with stem cells will no explain science to the general public, each of these eight-page doubt make important contributions to this breakthrough. documents traces the path leading to a breakthrough of great But the research outlined in this volume is equally certain to human benefit—such as the global positioning system (GPS) contribute to cures for cancer and for a large number of other or the cure for childhood leukemia. In every case, the final less famous diseases—many of mysterious origin—that are discovery depended on knowledge developed over decades terrible afflictions for humanity. xix

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New discoveries in the field of stem cell research have frequently appeared in the news and in scientific literature. Research in this area promises to lead to new therapies for cancer, heart disease, diabetes, and a wide variety of other diseases. This two-volume reference integrates this exciting
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