Sphingosine-1-Phosphate And Its Receptors Affect Cell Survival Of Human Umbilical Cord Mesenchymal Stem Cells

Stem cells are the specialized cells with the ability of self-renewel,possess varied potency and differentiate into multilineages.Because of clinical applications and biological importance,stem cell become a prominent subject in modern research era.Human umbilical cord mesenchymal stem cells(hUC-MSCs) are most promising candidates for cell-based therapies in diverse conditions including tissue engineering.MSCs,also known as multipotent cells,they are self-renewable,multipotent,homeing ability,its role in the treatment of chronic diseases and its use in human clinical trials are very important.Sphingosine-l-phosphate(S1P) is a bioactive sphingolipid metabolite formed by the phosphorylation of sphingosine by sphingosine kinase.S1P also is the ligand of a family of five specific G protein-coupled receptors that are differentially expressed in different tissues and regulate diverse cellular actions.These SIP receptors couple to multiple G-proteins to regulate intracellular signaling pathways.Therefore,S1P is known as a multifunctional physiologic mediator play an important role in the regulation of cell proliferation,survival,and cell death.Our preliminary study were show that SIP promotes the proliferation of hU-MSCs without variation on the expression of hU-MSCs surface markers.Our results provide a strong evidence to the cell transplantation therapy of long cell cycle and low survival rate of stem cells,which has wide prospect on clinical medicine.Moreover,S1P as a bioactive small molecular lack of immunogenicity,this character can useful to develop the serum-free culture system for hU-MSCs culture.Our study main to explore sphingosine-1-phosphate and his receptors on the effects of umbilical cord mesenchymal stem cells survival. We combined cell morphology and cell surface markers detection to identify hU-MSCs.The mRNA expression level of different SIP receptors in hU-MSCs was detected by real time PCR,discovering S1PR2 preferentially expressed.MTT assay was used to measure the proliferation of hU-MSCs induced by S1P,comparing to the control group,S1P can enhanced hU-MSCs proliferation.The migration ability was measured by Micro chemotoxic chamber assay with different concentrations of SIP stimulated hU-MSCs,found SIP inhibits hU-MSCs migration in a dose-dependent manner.Finally,use SIP receptor antagonist JTE-013 to discuss SIP via S1PR2 depress cell apoptosis and promote cell survival.