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

Journal of Biomedical Science

Ming Lei³  Jian R Lu¹  Henggui Zhang¹  Tan Wang²  Meihua Cai²  Fang Pan¹  Xiubo Zhao¹  Zhibin Chen²  Zhenqiang Zhao² 

[1] Biological Physics Group, School of Physics and Astronomy, University of Manchester, M139PL, UK;Department of Neurology, Affiliated Hospital, Hainan Medical College, Haikou, 570102, PR of China;Cardiovascular and Genetic Medicine Research Groups, School of Biomedicine, University of Manchester, Manchester, M13 9NT, UK

关键词: engineered cell sheets;    sphingosine-1-phosphate;    umbilical cord mesenchymal stem cells;   

Others  :  833467
DOI  :  10.1186/1423-0127-18-37

 received in 2011-03-06, accepted in 2011-06-07,  发布年份 2011

【 摘 要 】

Background

It is of growing interest to develop novel approaches to initiate differentiation of mesenchymal stem cells (MSCs) into cardiomyocytes. The purpose of this investigation was to determine if Sphingosine-1-phosphate (S1P), a native circulating bioactive lipid metabolite, plays a role in differentiation of human umbilical cord mesenchymal stem cells (HUMSCs) into cardiomyocytes. We also developed an engineered cell sheet from these HUMSCs derived cardiomyocytes by using a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm) cell sheet technology.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2011 Zhao et al; licensee BioMed Central Ltd.

【 图 表 】

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