Human adult skeletal muscle stem cells differentiate into cardiomyocyte phenotype in vitro |
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Authors: | Invernici Gloria Cristini Silvia Madeddu Paolo Brock Stefano Spillmann Frank Bernasconi Pia Cappelletti Cristina Calatozzolo Chiara Fascio Umberto Bisleri Gianluigi Muneretto Claudio Alessandri Giulio Parati Eugenio A |
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Institution: | Neurobiology and Neuroregenerative Therapies Unit, Fondazione IRCCS Neurological Institute C. Besta, Milan #20133, Italy. gloria.invernici@istituto-besta.it |
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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. |
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Keywords: | SkmSCs skeletal muscle-derived stem cells CM control medium SCM stem-cell medium RA Retinoic Acid MI myocardial infarction ANP atrial natriuretic peptide HR heart rate ES embryonic stem cells LV left ventricle LVSP LV systolic pressure |
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