Lysophosphatidic acid enhances human umbilical cord mesenchymal stem cell viability without differentiation via LPA receptor mediating mannerReport as inadecuate




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Apoptosis

pp 1–14

First Online: 01 August 2017

Abstract

Human umbilical cord mesenchymal stem cells hUC-MSCs are potential stromal cells which are regarded as the most feasible stem cell group in cell therapy. The maintenance of cell survival without differentiation is important in cell transplantation and stem cell therapy. However, negative factors exist in cell transplantation. Lysophosphatidic acid LPA is a non-antigenic small molecule phospholipid which induced several fundamental cellular responses, such as cell proliferation, apoptosis and migration. In this study we aimed to explore the effects of LPA on the survival and differentiation of MSCs and its availability in cell therapy. We found that LPA stimulated hUC-MSC proliferation and protected hUC-MSCs from lipopolysaccharide LPS induced apoptosis. We also observed that CD29, CD44, CD73, CD90 and CD105 were expressed, whereas CD34 and CD45 were not expressed in hUC-MSCs, and these makers have no change in LPA containing medium, which indicated that LPA accelerated the survival of hUC-MSCs in an undifferentiating status. We also demonstrated that higher expressed LPAR1 involved in LPA stimulated cell survival action. LPA stimulated cell proliferation was associated with LPAR1 mediated Gi-o-proteins-ERK1-2 pathway. On the other hand, LPA protected hUC-MSCs from LPS-induced apoptosis through suppressing caspase-3 activation by LPAR1 coupled with a G protein, but not Gi-o or Gq-11 in hUC-MSC. Collectively, this study demonstrated that LPA increased the proliferation and survival of hUC-MSCs without differentiation through LPAR1 mediated manner. Our findings provide that LPA as a anti-apoptotic agent having potential application prospect in cell transplantation and stem cell therapy.

KeywordsLysophosphatidic acid Human umbilical cord mesenchymal stem cells Cell survival Cell-surface marker Receptor mediated signaling AbbreviationsAPSAmmonium persulfate

CDCluster of differentiation

DEPCDiethyl pyrocarbonate

EdgEndothelial differentiation gene

EGFEpidermal growth factor

ERK1-2Extracellular signal-regulated kinase 1-2

FGFFibroblast growth factor

GPCRG-protein coupled receptor

hUC-MSCsHuman umbilical cord mesenchymal stem cells

LPALysophosphatidic acid

LPSLipopolysaccharide

MAPKMitogen activated protein kinase

MTT3-4,5-Dimethylthiahiazo-z-y1-3,5-diphenytetrazoliumromide

NCNegative control

PDGFPlatelet derived growth factor

PTXPertussis toxin

siRNASmall interfering RNA

TEMEDTetramethylethylenediamine

Li Narengerile and Yan Ya-Li have contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s10495-017-1399-6 contains supplementary material, which is available to authorized users.

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Author: Narengerile Li - Ya-Li Yan - Sachaofu Fu - Rui-Juan Li - Peng-Fei Zhao - Xi-Yuan Xu - Jing-Ping Yang - Alatangaole Damirin

Source: https://link.springer.com/







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