Abstract
Human umbilical cord mesenchymal stem cells (hUCMSCs) and human adipose tissue mesenchymal stem cells (hATMSCs) have the potential to differentiate into cardiomyocytes, making them promising therapeutic candidates for treating damaged cardiac tissues. Currently, however, the differentiated cells induced from hUCMSCs or hATMSCs can hardly display functional characteristics similar to cardiomyocytes. In this study, we have investigated the effects of bioactive lipid sphingosine‐1‐phosphate (S1P) on cardiac differentiations of hUCMSCs and hATMSCs in condition medium composed of cardiac myocytes culture medium or 5‐azacytidine. Cardiac differentiations were identified through immunofluorescence staining, and the results were observed with fluorescence microscopy and confocal microscopy. Synergistic effects of S1P and condition medium on cell viability were evaluated by MTT assays. Functional characteristics similar to cardiomyocytes were evaluated through detecting calcium transient. The differentiated hUCMSCs or hATMSCs in each group into cardiomyocytes showed positive expressions of cardiac specific proteins, including α‐actin, connexin‐43 and myosin heavy chain‐6 (MYH‐6). MTT assays showed that suitable differentiation time was 14 days and that the optimal concentration of S1P was 0.5 μM. Moreover, incorporation of S1P and cardiac myocytes culture medium gave rise to calcium transients, an important marker for displaying in vivo electrophysiological properties. This feature was not observed in the S1P‐5‐azacytidine group, indicating the possible lack of cellular stimuli such as transforming growth factor‐beta, TGF‐β. © 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd.
Highlights
Mesenchymal stem cells (MSCs) have the ability to differentiate into various types of tissue cells
The results of the two negative controls showed that human umbilical cord mesenchymal stem cells (hUCMSCs) (Figure S1B) and human adipose tissue mesenchymal stem cells (hATMSCs) (Figure S1C) had no expression of the three cardiac specific proteins (α-actin, connexin-43 and myosin heavy chain-6 (MYH-6)), while HCM cells expressed all of them (Figure S1A)
Differentiations of hATMSCs and hUCMSCs in each group into cardiomyocytes were undertaken and evaluated by immunofluorescence staining of cardiac specific proteins (α-actin, connexin-43 and MYH-6) on the 7th, 14th and 28th day, respectively
Summary
Mesenchymal stem cells (MSCs) have the ability to differentiate into various types of tissue cells. This property is of enormous potential to clinical applications in tissue regeneration covering bone, cartilage, muscle and adipose.[1,2,3] A number of recent reports have shown that MSCs could differentiate into cardiomyocytes in vivo and in vitro.[4,5]. Two types of MSCs, human umbilical cord mesenchymal stem cells (hUCMSCs) and human adipose tissue mesenchymal stem cells (hATMSCs), have been confirmed to possess the characteristics similar to MSCs from other sources. It is important to find a bioactive factor combining with cardiac differentiation medium for hUCMSCs or hATMSCs to improve their functional cardiomyogenic differentiation
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