title: Direct cardiac reprogramming: progress and challenges in basic biology and clinical applications.
abstract: The discovery of induced pluripotent stem cells changed the field of regenerative medicine and inspired the technological development of direct reprogramming or the process by which one cell type is directly converted into another without reverting a stem cell state by overexpressing lineage-specific factors. Indeed, direct reprogramming has proven sufficient in yielding a diverse range of cell types from fibroblasts, including neurons, cardiomyocytes, endothelial cells, hematopoietic stem/progenitor cells, and hepatocytes. These studies revealed that somatic cells are more plastic than anticipated, and that transcription factors, microRNAs, epigenetic factors, secreted molecules, as well as the cellular microenvironment are all important for cell fate specification. With respect to the field of cardiology, the cardiac reprogramming presents as a novel method to regenerate damaged myocardium by directly converting endogenous cardiac fibroblasts into induced cardiomyocyte-like cells in situ. The first in vivo cardiac reprogramming reports were promising to repair infarcted hearts; however, the low induction efficiency of fully reprogrammed, functional induced cardiomyocyte-like cells has become a major challenge and hampered our understanding of the reprogramming process. Nevertheless, recent studies have identified several critical factors that may affect the efficiency and quality of cardiac induction and have provided new insights into the mechanisms of cardiac reprogramming. Here, we review the progress in direct reprogramming research and discuss the perspectives and challenges of this nascent technology in basic biology and clinical applications.
authors: From the Department of Cardiology, Keio University School of Medicine, Japan Science and Technology CREST, Tokyo, Japan (T.S., M.I.); Japan Science and Technology CREST, Tokyo, Japan (M.I.); Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan (S.Y.); and Gladstone Institute of Cardiovascular Disease, San Francisco, CA (S.Y.).
authors: Taketaro
authors: T
authors: Sadahiro
authors: From the Department of Cardiology, Keio University School of Medicine, Japan Science and Technology CREST, Tokyo, Japan (T.S., M.I.); Japan Science and Technology CREST, Tokyo, Japan (M.I.); Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan (S.Y.); and Gladstone Institute of Cardiovascular Disease, San Francisco, CA (S.Y.).
authors: Shinya
authors: S
authors: Yamanaka
authors: From the Department of Cardiology, Keio University School of Medicine, Japan Science and Technology CREST, Tokyo, Japan (T.S., M.I.); Japan Science and Technology CREST, Tokyo, Japan (M.I.); Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan (S.Y.); and Gladstone Institute of Cardiovascular Disease, San Francisco, CA (S.Y.). mieda@z8.keio.jp.
authors: Masaki
authors: M
authors: Ieda
mesh_terms: D000818:Animals; D019070:Cell Lineage; D065150:Cellular Reprogramming; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D010641:Phenotype; D012038:Regeneration; D044968:Regenerative Medicine / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014157:Transcription Factors
keywords: fibroblasts; induced pluripotent stem cells; myocytes, cardiac