Sphingosine-1-phosphate promotes the differentiation of human umbilical cord mesenchymal stem cells into cardiomyocytes under the designated culturing conditions

Cardiomyogenic differentiation of HUMSCs was performed by culturing these cells with either designated cardiomyocytes conditioned medium (CMCM) alone, or with 1 μM S1P; or DMEM with 10% FBS + 1 μM S1P. Cardiomyogenic differentiation was determined by immunocytochemical analysis of expression of cardiomyocyte markers and patch clamping recording of the action potential.A cardiomyocyte-like morphology and the expression of α-actinin and myosin heavy chain (MHC) proteins can be observed in both CMCM culturing or CMCM+S1P culturing groups after 5 days' culturing, however, only the cells in CMCM+S1P culture condition present cardiomyocyte-like action potential and voltage gated currents. A new approach was used to form PIPAAm based temperature-responsive culture surfaces and this successfully produced cell sheets from HUMSCs derived cardiomyocytes.This study for the first time demonstrates that S1P potentiates differentiation of HUMSCs towards functional cardiomyocytes under the designated culture conditions. Our engineered cell sheets may provide a potential for clinically applicable myocardial tissues should promote cardiac tissue engineering research.Mesenchymal Stem cells (MSCs) are pluripotent cells that are able to differentiate into various specific cell types. Because of their plasticity, MSCs have been suggested as potential therapies for numerous diseases and conditions. In vitro differentiation of MSCs into cardiomyocytes offers a new cellular therapy for heart diseases. Therefore, it is of growing interest to develop novel approaches to initiate differentiation of various types of MSCs into cardiomyocytes. Human umbilical cord (UC) has been a tissue of increasing interest for such purpose due to the MSCs potency of stromal cells isolated from the human UC mesenchymal tissue, namely, Wharton's jelly[1]. A number of recent studies have shown that HUMSCs are able to differentiate towards multiple lineages including neuronal and myocardiogenic cells in vitro, thu