title: Direct Reprogramming-The Future of Cardiac Regeneration?
abstract: Today, the only available curative therapy for end stage congestive heart failure (CHF) is heart transplantation. This therapeutic option is strongly limited by declining numbers of available donor hearts and by restricted long-term performance of the transplanted graft. The disastrous prognosis for CHF with its restricted therapeutic options has led scientists to develop different concepts of alternative regenerative treatment strategies including stem cell transplantation or stimulating cell proliferation of different cardiac cell types in situ. However, first clinical trials with overall inconsistent results were not encouraging, particularly in terms of functional outcome. Among other approaches, very promising ongoing pre-clinical research focuses on direct lineage conversion of scar fibroblasts into functional myocardium, termed "direct reprogramming" or "transdifferentiation." This review seeks to summarize strategies for direct cardiac reprogramming including the application of different sets of transcription factors, microRNAs, and small molecules for an efficient generation of cardiomyogenic cells for regenerative purposes.
authors.affiliation: Division of Experimental Surgery, Department of Cardiovascular Surgery, Deutsches Herzzentrum München, Technische Universität München (TUM), Munich 80636, Germany. doppler@dhm.mhn.de.
authors.forename: Stefanie A
authors.initials: SA
authors.lastname: Doppler
authors.affiliation: Division of Experimental Surgery, Department of Cardiovascular Surgery, Deutsches Herzzentrum München, Technische Universität München (TUM), Munich 80636, Germany. deutsch@dhm.mhn.de.
authors.forename: Marcus-André
authors.initials: MA
authors.lastname: Deutsch
authors.affiliation: Division of Experimental Surgery, Department of Cardiovascular Surgery, Deutsches Herzzentrum München, Technische Universität München (TUM), Munich 80636, Germany. lange@dhm.mhn.de.|DZHK (German Center for Cardiovascular Research)-Partner Site Munich Heart Alliance, Munich 80802, Germany. lange@dhm.mhn.de.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Lange
authors.affiliation: Division of Experimental Surgery, Department of Cardiovascular Surgery, Deutsches Herzzentrum München, Technische Universität München (TUM), Munich 80636, Germany. krane@dhm.mhn.de.|DZHK (German Center for Cardiovascular Research)-Partner Site Munich Heart Alliance, Munich 80802, Germany. krane@dhm.mhn.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Krane
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015316:Genetic Therapy; D006333:Heart Failure / Q000235:genetics / Q000628:therapy*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D012038:Regeneration; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D014157:Transcription Factors
keywords: Gata4, Mef2c, Tbx5 (GMT); direct reprogramming; induced cardiomyocytes (iCMs); transdifferentiation