Abstract
Adipose-derived stromal cells (ADSCs) represent a readily available abundant supply of mesenchymal stem cells and have the ability to differentiate into cardiomyocytes in mice and human, making ADSCs a promising source of cardiomyocytes for transplantation. However, there has been no report of differentiation of rat ADSCs into cardiomyocytes. In addition, signaling pathways in the differentiation process from ADSCs to cardiomyocytes are unknown. In this study, we first demonstrated that rat ADSCs spontaneously differentiated into cardiomyocytes in vitro, when cultured on a complete medium formulation MethoCult GF M3534. These differentiated cells possessed cardiomyocyte phenotype and expressed cardiac markers. Moreover, these cells showed open excitation-contracting coupling and Ca2+ transient and contracted spontaneously. The role of Rho-associated protein kinases (ROCKs) in the differentiation process was then studied by using ROCK-specific inhibitor Y-27632 and ROCK siRNAs. These agents changed the arrangement of cytoskeleton and diminished appearance of cardiomyocyte phenotype, accompanied by inhibition of c-Jun N-terminal kinase (JNK) phosphorylation and promotion of Akt phosphorylation. Collectively, this is the first study to demonstrate that rat ADSCs could spontaneously differentiate into cardiomyocytes in vitro and ROCKs play an important role in the differentiation of ADSCs into beating cardiomyocytes in conjunction of the PI3K/Akt pathway and the JNK pathway.
Highlights
Myocardial infarction (MI) afflicts millions of people each year
To induce the differentiation of adipose tissue-derived stromal cells (ADSCs) into beating cardiomyocytes, isolated stromal vascular fraction (SVF) cells were directly plated in the semisolid methylcellulose medium MethoCult GF M3534
We found in the absence or presence of Y-27632 did not alter the time course of ADSCs intocardiomyocytes differentiation
Summary
Myocardial infarction (MI) afflicts millions of people each year. It causes a significant amount of deaths, especially in developed countries and increasingly more in developing countries. Cell transplantation and gene transfer are two of the foremost therapies with a potential for regenerating damaged cardiomyocytes and enabling revascularization. Adipose tissue-derived stromal cells (ADSCs) represent an abundant, practical and appealing source of donor tissue for autologous cell replacement for ischemic heart diseases [1]. Cultured ADSCs can be differentiated into adipogenic, osteogenic, chondrogenic, and myogenic cells under certain conditions [2, 3]. Adipose tissue is an attractive cell source for stem cell-based treatment of injured myocardium because it is relatively easy to harvest from patients by a simple, minimally invasive method, available in sufficient quantities and cultured
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
