title: Sphingosine-1-phosphate promotes the differentiation of human umbilical cord mesenchymal stem cells into cardiomyocytes under the designated culturing conditions.
abstract: 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.
authors.affiliation: Department of Neurology, Affiliated Hospital, Hainan Medical College, Haikou, P.R. China.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Chen
authors.forename: Xiubo
authors.initials: X
authors.lastname: Zhao
authors.forename: Fang
authors.initials: F
authors.lastname: Pan
authors.forename: Meihua
authors.initials: M
authors.lastname: Cai
authors.forename: Tan
authors.initials: T
authors.lastname: Wang
authors.forename: Henggui
authors.initials: H
authors.lastname: Zhang
authors.forename: Jian R
authors.initials: JR
authors.lastname: Lu
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000180:Acrylic Resins; D000185:Actinin / Q000378:metabolism; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000166:cytology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D000178:Acrylamides; D000180:Acrylic Resins; D008246:Lysophospholipids; D011108:Polymers; D000185:Actinin; C052970:poly-N-isopropylacrylamide; C060506:sphingosine 1-phosphate; D018995:Myosin Heavy Chains; D013110:Sphingosine