Clinical Application of Induced Pluripotent Stem Cells in Cardiovascular Medicine

Induced pluripotent stem cells (iPSCs) are generated by reprogramming human somatic cells through the overexpression of four transcription factors: Oct4, Sox2, Klf4 and c-Myc. iPSCs are capable of indefinite self-renewal, and they can differentiate into almost any type of cell in the body. These cells therefore offer a highly valuable therapeutic strategy for tissue repair and regeneration. Recent experimental and preclinical research has revealed their potential for cardiovascular disease diagnosis, drug screening and cellular replacement therapy. Nevertheless, significant challenges remain in terms of the development and clinical application of human iPSCs. Here, we review current progress in research related to patient-specific iPSCs for ex vivo modeling of cardiovascular disorders and drug screening, and explore the potential of human iPSCs for use in the field of cardiovascular regenerative medicine.

[1]  Philip Wong,et al.  Generation of patient-specific induced pluripotent stem cell-derived cardiomyocytes as a cellular model of arrhythmogenic right ventricular cardiomyopathy. , 2013, European heart journal.

[2]  S. Yuasa,et al.  Novel insights into disease modeling using induced pluripotent stem cells. , 2013, Biological & pharmaceutical bulletin.

[3]  M. Suematsu,et al.  Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell-derived cardiomyocytes. , 2013, Cell stem cell.

[4]  Takashi Daimon,et al.  Feasibility, Safety, and Therapeutic Efficacy of Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Sheets in a Porcine Ischemic Cardiomyopathy Model , 2012, Circulation.

[5]  Shinsuke Yuasa,et al.  Disease characterization using LQTS-specific induced pluripotent stem cells. , 2012, Cardiovascular research.

[6]  Euan A. Ashley,et al.  Patient-Specific Induced Pluripotent Stem Cells as a Model for Familial Dilated Cardiomyopathy , 2012, Science Translational Medicine.

[7]  Laura Iop,et al.  Dantrolene rescues arrhythmogenic RYR2 defect in a patient-specific stem cell model of catecholaminergic polymorphic ventricular tachycardia , 2012, EMBO molecular medicine.

[8]  Ofer Binah,et al.  Cardiomyocytes generated from CPVTD307H patients are arrhythmogenic in response to β-adrenergic stimulation , 2012, Journal of cellular and molecular medicine.

[9]  K. Christman,et al.  Biomaterials for the treatment of myocardial infarction: a 5-year update. , 2011, Journal of the American College of Cardiology.

[10]  Katriina Aalto-Setälä,et al.  Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture , 2011, Disease Models & Mechanisms.

[11]  S. Yuasa,et al.  Induced Pluripotent Stem Cells in Cardiovascular Medicine , 2011, Stem cells international.

[12]  B. Strauer,et al.  10 years of intracoronary and intramyocardial bone marrow stem cell therapy of the heart: from the methodological origin to clinical practice. , 2011, Journal of the American College of Cardiology.

[13]  K. Fukuda,et al.  Safety and efficacy of pericardial endoscopy by percutaneous subxyphoid approach in swine heart in vivo. , 2011, The Journal of thoracic and cardiovascular surgery.

[14]  Carl-Fredrik Mandenius,et al.  Cardiotoxicity testing using pluripotent stem cell‐derived human cardiomyocytes and state‐of‐the‐art bioanalytics: a review , 2011, Journal of applied toxicology : JAT.

[15]  Jonathan A. Bernstein,et al.  Using iPS cells to investigate cardiac phenotypes in patients with Timothy Syndrome , 2011, Nature.

[16]  Lior Gepstein,et al.  Modelling the long QT syndrome with induced pluripotent stem cells , 2011, Nature.

[17]  M. Pera,et al.  Stem cells: The dark side of induced pluripotency , 2011, Nature.

[18]  Divya Rajamohan,et al.  Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation , 2011, European heart journal.

[19]  Jarrett Rosenberg,et al.  Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells. , 2011, The Journal of clinical investigation.

[20]  Gang Wang,et al.  Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy , 2011, Nature Cell Biology.

[21]  Beau R. Webber,et al.  Hematopoietic differentiation of induced pluripotent stem cells from patients with mucopolysaccharidosis type I (Hurler syndrome). , 2011, Blood.

[22]  E. Callaway Cells snag top modelling job , 2011, Nature.

[23]  Zongjin Li,et al.  Functional characterization and expression profiling of human induced pluripotent stem cell- and embryonic stem cell-derived endothelial cells. , 2011, Stem cells and development.

[24]  Jinqiu Zhang,et al.  A human iPSC model of Hutchinson Gilford Progeria reveals vascular smooth muscle and mesenchymal stem cell defects. , 2011, Cell stem cell.

[25]  Ronald A. Li,et al.  Proarrhythmic risk of embryonic stem cell-derived cardiomyocyte transplantation in infarcted myocardium. , 2010, Heart rhythm.

[26]  Fred H. Gage,et al.  A Model for Neural Development and Treatment of Rett Syndrome Using Human Induced Pluripotent Stem Cells , 2010, Cell.

[27]  D. Pei,et al.  Induced Pluripotent Stem Cells Can Be Used to Model the Genomic Imprinting Disorder Prader-Willi Syndrome* , 2010, The Journal of Biological Chemistry.

[28]  M. Seyfarth,et al.  Patient-specific induced pluripotent stem-cell models for long-QT syndrome. , 2010 .

[29]  Stormy J. Chamberlain,et al.  Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader–Willi syndromes , 2010, Proceedings of the National Academy of Sciences.

[30]  V. Vedantham,et al.  Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors , 2010, Cell.

[31]  A. Mathur,et al.  Cardiac stem cell therapy: progress from the bench to bedside , 2010, Heart.

[32]  S. Yamanaka,et al.  Recent Stem Cell Advances: Induced Pluripotent Stem Cells for Disease Modeling and Stem Cell–Based Regeneration , 2010, Circulation.

[33]  D. Mastroeni,et al.  Transplantation of cardiac progenitor cell sheet onto infarcted heart promotes cardiogenesis and improves function. , 2010, Cardiovascular research.

[34]  G. Daley,et al.  Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. , 2010, Cell stem cell.

[35]  Zhaohui Ye,et al.  Generation of endoderm‐derived human induced pluripotent stem cells from primary hepatocytes , 2010, Hepatology.

[36]  Clive N. Svendsen,et al.  Human stem cells and drug screening: opportunities and challenges , 2010, Nature Reviews Drug Discovery.

[37]  M. Tada,et al.  Progressive maturation in contracting cardiomyocytes derived from human embryonic stem cells: Qualitative effects on electrophysiological responses to drugs. , 2010, Stem cell research.

[38]  Robert Passier,et al.  Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes. , 2010, Stem cell research.

[39]  J. Augoustides,et al.  Recent progress in heart failure treatment and heart transplantation. , 2009, Journal of cardiothoracic and vascular anesthesia.

[40]  Jehyuk Lee,et al.  Generation of functional human hepatic endoderm from human induced pluripotent stem cells , 2009, Hepatology.

[41]  Tetsuo Sasano,et al.  Engraftment, Differentiation, and Functional Benefits of Autologous Cardiosphere-Derived Cells in Porcine Ischemic Cardiomyopathy , 2009, Circulation.

[42]  M. Murata,et al.  Omentopexy enhances graft function in myocardial cell sheet transplantation. , 2009, Biochemical and biophysical research communications.

[43]  Xiaolei Yin,et al.  Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells , 2009, Cell Research.

[44]  Shinsuke Yuasa,et al.  In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. , 2009, Biochemical and biophysical research communications.

[45]  Masayuki Yamato,et al.  Cell sheet-based myocardial tissue engineering: new hope for damaged heart rescue. , 2009, Current pharmaceutical design.

[46]  D. Roberts,et al.  Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages , 2009, Nature.

[47]  A. Consiglio,et al.  Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells , 2009, Nature.

[48]  Y. Kan,et al.  Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases , 2009, Proceedings of the National Academy of Sciences.

[49]  P. Menasché Stem cell therapy for heart failure: are arrhythmias a real safety concern? , 2009, Circulation.

[50]  James A. Thomson,et al.  Induced pluripotent stem cells from a spinal muscular atrophy patient , 2009, Nature.

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

[52]  Jason D. Christie,et al.  Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult heart transplant report--2008. , 2008, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

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

[54]  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 .

[55]  J. Byrne Generation of isogenic pluripotent stem cells. , 2008, Human molecular genetics.

[56]  O. Alfieri,et al.  The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First Randomized Placebo-Controlled Study of Myoblast Transplantation , 2008, Circulation.

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

[58]  T. Hartung,et al.  First steps in establishing a developmental toxicity test method based on human embryonic stem cells. , 2008, Toxicology in vitro : an international journal published in association with BIBRA.

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

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

[61]  Marius Wernig,et al.  Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin , 2007, Science.

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

[63]  P. Doevendans,et al.  Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction. , 2007, Stem cell research.

[64]  L. Gepstein,et al.  Identification and selection of cardiomyocytes during human embryonic stem cell differentiation , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[65]  M. Bobbert Ethical questions concerning research on human embryos, embryonic stem cells and chimeras , 2006, Biotechnology journal.

[66]  Randall J Lee,et al.  Biomaterials for the treatment of myocardial infarction. , 2006, Journal of the American College of Cardiology.

[67]  Dan M. Roden,et al.  ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines , 2006 .

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

[69]  Keiichi Fukuda,et al.  Pulsatile Cardiac Tissue Grafts Using a Novel Three-Dimensional Cell Sheet Manipulation Technique Functionally Integrates With the Host Heart, In Vivo , 2006, Circulation research.

[70]  A. Jemal,et al.  Trends in the leading causes of death in the United States, 1970-2002. , 2005, JAMA.

[71]  Shinsuke Yuasa,et al.  Analysis of the electrophysiological properties and arrhythmias in directly contacted skeletal and cardiac muscle cell sheets. , 2005, Cardiovascular research.

[72]  Icilio Cavero,et al.  ICH S7B draft guideline on the non-clinical strategy for testing delayed cardiac repolarisation risk of drugs: a critical analysis , 2005, Expert opinion on drug safety.

[73]  M. Suematsu,et al.  Purified cardiomyocytes from bone marrow mesenchymal stem cells produce stable intracardiac grafts in mice. , 2005, Cardiovascular research.

[74]  D. Torella,et al.  Adult Cardiac Stem Cells Are Multipotent and Support Myocardial Regeneration , 2003, Cell.

[75]  E. Audinat,et al.  Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[76]  A. Hagège,et al.  Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. , 2003, Journal of the American College of Cardiology.

[77]  A. Hagège,et al.  Long-term (1 year) functional and histological results of autologous skeletal muscle cells transplantation in rat. , 2003, Cardiovascular research.

[78]  F. Pagani,et al.  Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. , 2003, Journal of the American College of Cardiology.

[79]  Alon Spira,et al.  High-Resolution Electrophysiological Assessment of Human Embryonic Stem Cell-Derived Cardiomyocytes: A Novel In Vitro Model for the Study of Conduction , 2002, Circulation research.

[80]  A. Hagège,et al.  Long-Term Efficacy of Myoblast Transplantation on Regional Structure and Function After Myocardial Infarction , 2002, Circulation.

[81]  D. Sawyer,et al.  Cell Therapy Attenuates Deleterious Ventricular Remodeling and Improves Cardiac Performance After Myocardial Infarction , 2001, Circulation.

[82]  David M. Bodine,et al.  Bone marrow cells regenerate infarcted myocardium , 2001, Nature.

[83]  A. Hagège,et al.  Myoblast transplantation for heart failure , 2001, The Lancet.

[84]  C. Murry,et al.  Transmural replacement of myocardium after skeletal myoblast grafting into the heart. Too much of a good thing? , 2000, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

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

[86]  W. Allan,et al.  Long QT Syndrome , 1998, Pediatrics.

[87]  I. Temple,et al.  Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic lentiginosis). , 1997, Journal of medical genetics.

[88]  遠山 周吾 Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell-derived cardiomyocytes , 2013 .

[89]  E. Sasaki,et al.  Nongenetic method for purifying stem cell–derived cardiomyocytes , 2010, Nature Methods.

[90]  Yongchao Ge,et al.  Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome , 2010 .

[91]  A. Terzic,et al.  Repair of Acute Myocardial Infarction by Human Stemness Factors Induced Pluripotent Stem Cells , 2009 .

[92]  S. Kattman,et al.  Directed differentiation of pluripotent stem cells: from developmental biology to therapeutic applications. , 2008, Cold Spring Harbor symposia on quantitative biology.

[93]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.

[94]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .