title: Human adult skeletal muscle stem cells differentiate into cardiomyocyte phenotype in vitro.
abstract: Cell transplantation to repair or regenerate injured myocardium is a new frontier in the treatment of cardiovascular disease. Most studies on stem cell transplantation therapy in both experimental heart infarct and in phase-I human clinical trials have focused on the use of undifferentiated stem cells. Based on our previous observations demonstrating the presence of multipotent progenitor cells in human adult skeletal muscle, in this study we investigated the capacity of these progenitors to differentiate into cardiomyocytes. Here we show an efficient protocol for the cardiomyogenic differentiation of human adult skeletal muscle stem cells in vitro. We found that treatment with Retinoic Acid directed cardiomyogenic differentiation of skeletal muscle stem cells in vitro. After Retinoic Acid treatment, cells expressed cardiomyocyte markers and acquired spontaneous contraction. Functional assays exhibited cardiac-like response to increased extracellular calcium. When cocultured with mouse cardiomyocytes, Retinoic Acid-treated skeletal muscle stem cells expressed connexin43 and when transplanted into ischemic heart were detectable even 5 weeks after injection. Based on these results, we can conclude that human adult skeletal muscle stem cells, if opportunely treated, can transdifferentiate into cells of cardiac lineage and once injected into infarcted heart can integrate, survive in cardiac tissue and improve the cardiac function.
authors: Neurobiology and Neuroregenerative Therapies Unit, Fondazione IRCCS Neurological Institute C. Besta, Milan #20133, Italy. gloria.invernici@istituto-besta.it
authors: Gloria
authors: G
authors: Invernici
authors: Silvia
authors: S
authors: Cristini
authors: Paolo
authors: P
authors: Madeddu
authors: Stefano
authors: S
authors: Brock
authors: Frank
authors: F
authors: Spillmann
authors: Pia
authors: P
authors: Bernasconi
authors: Cristina
authors: C
authors: Cappelletti
authors: Chiara
authors: C
authors: Calatozzolo
authors: Umberto
authors: U
authors: Fascio
authors: Gianluigi
authors: G
authors: Bisleri
authors: Claudio
authors: C
authors: Muneretto
authors: Giulio
authors: G
authors: Alessandri
authors: Eugenio A
authors: EA
authors: Parati
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000077214:Becaplermin; D002454:Cell Differentiation; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D014212:Tretinoin