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Human cardiac tissue induces transdifferentiation of adult stem cells towards cardiomyocytes
Macarena Perán?1,2*, Juan A. Marchal?2,3*, Elena López?2, Manuel Jiménez-Navarro?4, Houria Boulaiz?2,3, Fernando Rodríguez-Serrano?2,3, Esmeralda Carrillo?2,3, Gema Sánchez-Espin?4, Eduardo de Teresa?4, David Tosh?5 & Antonia Aranega?2,3
Department of Health Sciences, University of Jaén, Spain
Biopathology and Medicine Regenerative Institute (IBIMER), Granada, Spain
Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Spain
Heart Unit, Virgen de la Victoria, Clinical University Hospital, Málaga, Spain
Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, UK
*These authors contributed equally to this work
Background aims. The goal was to induce the transdifferentiation (or conversion) of human adipose-derived stem cells to cardiomyocytes using an intracellular extract obtained from adult human heart tissue. Methods. Human adult stem cells from lipoaspirates were transiently permeabilized, exposed to human atrial extracts and allowed to recover in culture. Results. After 21 days, the cells acquired a cardiomyocyte phenotype, as demonstrated by morphologic changes (appearance of binucleate, striated cells and branching fibers), immunofluorescence detection of cardiac-specific markers (connexin-43, sarcomeric α-actinin, cardiac troponin I and T, and desmin) and the presence of cardiomyocyte-related genes analyzed by reverse transcription–polymerase chain reaction (cardiac myosin light chain 1, α-cardiac actin, cardiac troponin T and cardiac β-myosin). Conclusions. We have demonstrated for the first time that adult cardiomyocytes obtained from human donors retain the capacity to induce cardiomyocyte differentiation of mesenchymal stromal cells. The use of autologous extracts for reprogramming adult stem cells may have potential therapeutic implications for treating heart disease.
