Stem Cell Platforms for Regenerative Medicine

The pandemic of chronic degenerative diseases associated with aging demographics mandates development of effective approaches for tissue repair. As diverse stem cells directly contribute to innate healing, the capacity for de novo tissue reconstruction harbors a promising role for regenerative medicine. Indeed, a spectrum of natural stem cell sources ranging from embryonic to adult progenitors has been recently identified with unique characteristics for regeneration. The accessibility and applicability of the regenerative armamentarium has been further expanded with stem cells engineered by nuclear reprogramming. Through strategies of replacement to implant functional tissues, regeneration to transplant progenitor cells or rejuvenation to activate endogenous self‐repair mechanisms, the overarching goal of regenerative medicine is to translate stem cell platforms into practice and achieve cures for diseases limited to palliative interventions. Harnessing the full potential of each platform will optimize matching stem cell‐based biologics with the disease‐specific niche environment of individual patients to maximize the quality of long‐term management, while minimizing the needs for adjunctive therapy. Emerging discovery science with feedback from clinical translation is therefore poised to transform medicine offering safe and effective stem cell biotherapeutics to enable personalized solutions for incurable diseases.

[1]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[2]  Z. Estrov,et al.  Adult stem cells for tissue repair - a new therapeutic concept? , 2003, The New England journal of medicine.

[3]  N. Rosenthal Prometheus's vulture and the stem-cell promise. , 2003, The New England journal of medicine.

[4]  Irving L Weissman,et al.  Plasticity of Adult Stem Cells , 2004, Cell.

[5]  Robert S Negrin,et al.  Hematopoietic stem and progenitor cells: clinical and preclinical regeneration of the hematolymphoid system. , 2005, Annual review of medicine.

[6]  S. Goldman Stem and progenitor cell–based therapy of the human central nervous system , 2005, Nature Biotechnology.

[7]  M. Surani,et al.  Stem cells: A new route to rejuvenation , 2006, Nature.

[8]  Rudolf Jaenisch,et al.  Nuclear reprogramming and pluripotency , 2006, Nature.

[9]  D. Solter,et al.  From teratocarcinomas to embryonic stem cells and beyond: a history of embryonic stem cell research , 2006, Nature Reviews Genetics.

[10]  M. Stojkovic,et al.  Epigenetic Modification Is Central to Genome Reprogramming in Somatic Cell Nuclear Transfer , 2006, Stem cells.

[11]  R. Benezra,et al.  Embryonic stem cells prevent developmental cardiac defects in mice , 2006, Nature Clinical Practice Cardiovascular Medicine.

[12]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[13]  R. Jaenisch,et al.  In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state , 2007, Nature.

[14]  Shulan Tian,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[15]  J. Cibelli,et al.  Interspecies nuclear transfer: implications for embryonic stem cell biology. , 2007, Cell stem cell.

[16]  Giselle Chamberlain,et al.  Concise Review: Mesenchymal Stem Cells: Their Phenotype, Differentiation Capacity, Immunological Features, and Potential for Homing , 2007, Stem cells.

[17]  A. Terzic,et al.  Molecular Medicine Hones Therapeutic Arts to Science , 2007, Clinical pharmacology and therapeutics.

[18]  S. Yamanaka Strategies and new developments in the generation of patient-specific pluripotent stem cells. , 2007, Cell stem cell.

[19]  M. Stojkovic,et al.  The status of human nuclear transfer , 2007, Stem Cell Reviews.

[20]  T. Ichisaka,et al.  Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2007, Cell.

[21]  D. Prockop,et al.  Concise Review: Mesenchymal Stem/Multipotent Stromal Cells: The State of Transdifferentiation and Modes of Tissue Repair—Current Views , 2007, Stem cells.

[22]  D. K. Arrell,et al.  Cardiopoietic programming of embryonic stem cells for tumor-free heart repair , 2007, The Journal of experimental medicine.

[23]  W. Sanger,et al.  Producing primate embryonic stem cells by somatic cell nuclear transfer , 2007, Nature.

[24]  M. Cairo,et al.  The potential of umbilical cord blood multipotent stem cells for nonhematopoietic tissue and cell regeneration. , 2007, Experimental hematology.

[25]  O. Ringdén,et al.  Immunomodulation by mesenchymal stem cells and clinical experience , 2007, Journal of internal medicine.

[26]  A. Caplan Adult mesenchymal stem cells for tissue engineering versus regenerative medicine , 2007, Journal of cellular physiology.

[27]  E. Horwitz,et al.  Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs. , 2007, Blood.

[28]  Marius Wernig,et al.  Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells , 2007, Nature Biotechnology.

[29]  H. Lewin,et al.  Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning , 2007, Nature Genetics.

[30]  J. Utikal,et al.  Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. , 2007, Cell stem cell.

[31]  T. Ichisaka,et al.  Generation of germline-competent induced pluripotent stem cells , 2007, Nature.

[32]  Anthony Atala,et al.  Isolation of amniotic stem cell lines with potential for therapy , 2007, Nature Biotechnology.

[33]  J. Rossant Stem Cells and Early Lineage Development , 2008, Cell.

[34]  C. Mummery,et al.  Origins and Fates of Cardiovascular Progenitor Cells , 2008, Cell.

[35]  N. Forraz,et al.  Potential for access to embryonic‐like cells from human umbilical cord blood , 2007, Cell proliferation.

[36]  George Q. Daley,et al.  Reprogramming of human somatic cells to pluripotency with defined factors , 2008, Nature.

[37]  Gordon Keller,et al.  Differentiation of Embryonic Stem Cells to Clinically Relevant Populations: Lessons from Embryonic Development , 2008, Cell.

[38]  L. Rubin Stem Cells and Drug Discovery: The Beginning of a New Era? , 2008, Cell.

[39]  George Q. Daley,et al.  Prospects for Stem Cell-Based Therapy , 2008, Cell.

[40]  Timothy J. Nelson,et al.  Embryonic Stem Cell Therapy of Heart Failure in Genetic Cardiomyopathy , 2008, Stem cells.

[41]  Shinya Yamanaka,et al.  Pluripotency and nuclear reprogramming , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[42]  G. Galbraith,et al.  In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state , 2008 .

[43]  Richard T. Lee,et al.  Stem-cell therapy for cardiac disease , 2008, Nature.

[44]  E. Kroon,et al.  Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo , 2008, Nature Biotechnology.

[45]  S. H. Wood,et al.  Development of Human Cloned Blastocysts Following Somatic Cell Nuclear Transfer with Adult Fibroblasts , 2008, Stem cells.

[46]  Timothy J. Nelson,et al.  CXCR4+/FLK‐1+ Biomarkers Select a Cardiopoietic Lineage from Embryonic Stem Cells , 2008, Stem cells.

[47]  K. Chien,et al.  Regenerative medicine and human models of human disease , 2008, Nature.

[48]  Hynek Wichterle,et al.  Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons , 2008, Science.

[49]  T. Ichisaka,et al.  Induction of Pluripotent Stem Cells From Adult Human Fibroblasts by Defined Factors , 2008 .

[50]  J. Knoblich,et al.  Mechanisms of Asymmetric Stem Cell Division , 2008, Cell.

[51]  I. Weissman,et al.  Stems Cells and the Pathways to Aging and Cancer , 2008, Cell.

[52]  Christine L. Mummery,et al.  Embryonic Stem (es) Cells from Mice and Primates Can Differentiate into Any Cell Type in the Adult Body Stem Cells in Fetal and Adult Hearts Stem-cell-based Therapy and Lessons from the Heart Insight Review , 2022 .

[53]  Ulrich H. von Andrian,et al.  Stem Cell Trafficking in Tissue Development, Growth, and Disease , 2008, Cell.

[54]  A. Terzic,et al.  Mesenchymal Stem Cells: Engineering Regeneration , 2008, Clinical and translational science.

[55]  A. Terzic,et al.  KCNJ11 knockout morula re-engineered by stem cell diploid aggregation , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[56]  A. Terzic,et al.  Stem Cells: Biologics for Regeneration , 2008, Clinical pharmacology and therapeutics.

[57]  Austin G Smith,et al.  Capturing Pluripotency , 2008, Cell.

[58]  N. Rosenthal,et al.  Derive and conquer: sourcing and differentiating stem cells for therapeutic applications , 2008, Nature Reviews Drug Discovery.

[59]  Sean J. Morrison,et al.  Stem Cells and Niches: Mechanisms That Promote Stem Cell Maintenance throughout Life , 2008, Cell.

[60]  S. Senju,et al.  Activation of Antigen-Specific Cytotoxic T Lymphocytes by β2-Microglobulin or TAP1 Gene Disruption and the Introduction of Recipient-Matched MHC Class I Gene in Allogeneic Embryonic Stem Cell-Derived Dendritic Cells1 , 2008, The Journal of Immunology.

[61]  George Q. Daley,et al.  Disease-Specific Induced Pluripotent Stem Cells , 2008, Cell.

[62]  F. Gage,et al.  Mechanisms and Functional Implications of Adult Neurogenesis , 2008, Cell.

[63]  A. Terzic,et al.  Strategies for Therapeutic Repair: The “R3” Regenerative Medicine Paradigm , 2008, Clinical and translational science.

[64]  Takashi Aoi,et al.  Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts , 2008, Nature Biotechnology.

[65]  Kathryn J Wood,et al.  Embryonic Stem Cells and Their Differentiated Derivatives Have a Fragile Immune Privilege but Still Represent Novel Targets of Immune Attack , 2008, Stem cells.

[66]  Paul H Lerou,et al.  Generation of human-induced pluripotent stem cells , 2008, Nature Protocols.

[67]  J. Platt,et al.  Immunosuppression by Embryonic Stem Cells , 2008, Stem cells.

[68]  A. Atala Advances in tissue and organ replacement. , 2008, Current stem cell research & therapy.

[69]  A. Terzic,et al.  Therapeutic Targeting: A Crucible for Individualized Medicine , 2008, Clinical pharmacology and therapeutics.

[70]  L. Zon,et al.  Hematopoiesis: An Evolving Paradigm for Stem Cell Biology , 2008, Cell.

[71]  R. Young,et al.  Stem Cells, the Molecular Circuitry of Pluripotency and Nuclear Reprogramming , 2008, Cell.

[72]  T. Cantz,et al.  Induced pluripotent stem cells generated without viral integration , 2009, Hepatology.