PMID- 28766061 OWN - NLM STAT- MEDLINE DCOM- 20180522 LR - 20181202 IS - 1573-675X (Electronic) IS - 1360-8185 (Print) IS - 1360-8185 (Linking) VI - 22 IP - 10 DP - 2017 Oct TI - Lysophosphatidic acid enhances human umbilical cord mesenchymal stem cell viability without differentiation via LPA receptor mediating manner. PG - 1296-1309 LID - 10.1007/s10495-017-1399-6 [doi] AB - 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 G(i/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 G(i/o) or G(q/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. FAU - Li, Narengerile AU - Li N AD - Department of Biology, College of Life Sciences, Inner Mongolia University, Hohhot, 010021, Inner Mongolia, China. AD - Department of Respiratory and Critical Medicine, The Third Affiliated Hospital, Inner Mongolia Medical University, Baotou, 014010, Inner Mongolia, China. FAU - Yan, Ya-Li AU - Yan YL AD - Department of Biology, College of Life Sciences, Inner Mongolia University, Hohhot, 010021, Inner Mongolia, China. FAU - Fu, Sachaofu AU - Fu S AD - Department of Biology, College of Life Sciences, Inner Mongolia University, Hohhot, 010021, Inner Mongolia, China. FAU - Li, Rui-Juan AU - Li RJ AD - Department of Biology, College of Life Sciences, Inner Mongolia University, Hohhot, 010021, Inner Mongolia, China. FAU - Zhao, Peng-Fei AU - Zhao PF AD - Department of Biology, College of Life Sciences, Inner Mongolia University, Hohhot, 010021, Inner Mongolia, China. FAU - Xu, Xi-Yuan AU - Xu XY AD - Department of Respiratory and Critical Medicine, The Third Affiliated Hospital, Inner Mongolia Medical University, Baotou, 014010, Inner Mongolia, China. FAU - Yang, Jing-Ping AU - Yang JP AD - Department of Respiratory and Critical Medicine, The Third Affiliated Hospital, Inner Mongolia Medical University, Baotou, 014010, Inner Mongolia, China. yangron@sina.com.cn. FAU - Damirin, Alatangaole AU - Damirin A AD - Department of Biology, College of Life Sciences, Inner Mongolia University, Hohhot, 010021, Inner Mongolia, China. bigaole@imu.edu.cn. LA - eng GR - No. 81460021/National Natural Science Foundation of China/International GR - No. 8166010065/National Natural Science Foundation of China/International GR - No.31260210/National Natural Science Foundation of China/International PT - Journal Article PL - Netherlands TA - Apoptosis JT - Apoptosis : an international journal on programmed cell death JID - 9712129 RN - 0 (Antigens, Differentiation) RN - 0 (GTP-Binding Protein alpha Subunits) RN - 0 (Lysophospholipids) RN - 0 (Receptors, Lysophosphatidic Acid) RN - EC 3.4.22.- (Caspase 3) RN - PG6M3969SG (lysophosphatidic acid) SB - IM MH - Antigens, Differentiation/genetics MH - Apoptosis/drug effects/physiology MH - Caspase 3/metabolism MH - Cell Differentiation/*drug effects MH - Cell Proliferation/drug effects/physiology MH - Cell Survival/*drug effects MH - Cells, Cultured MH - GTP-Binding Protein alpha Subunits/antagonists & inhibitors/metabolism MH - Gene Expression Regulation/drug effects MH - Gene Knockdown Techniques MH - Humans MH - Lysophospholipids/pharmacology/*physiology MH - MAP Kinase Signaling System/physiology MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology/*drug effects/metabolism MH - Receptors, Lysophosphatidic Acid/antagonists & inhibitors/genetics/*metabolism MH - Umbilical Cord/*cytology PMC - PMC5630659 OTO - NOTNLM OT - Cell survival OT - Cell-surface marker OT - Human umbilical cord mesenchymal stem cells OT - Lysophosphatidic acid OT - Receptor mediated signaling COIS- CONFLICT OF INTEREST: The authors declare that they have no conflict of interest. INFORMED CONSENT: Informed consent was obtained from all individual participants included in the study. EDAT- 2017/08/03 06:00 MHDA- 2018/05/23 06:00 PMCR- 2017/08/01 CRDT- 2017/08/03 06:00 PHST- 2017/08/03 06:00 [pubmed] PHST- 2018/05/23 06:00 [medline] PHST- 2017/08/03 06:00 [entrez] PHST- 2017/08/01 00:00 [pmc-release] AID - 10.1007/s10495-017-1399-6 [pii] AID - 1399 [pii] AID - 10.1007/s10495-017-1399-6 [doi] PST - ppublish SO - Apoptosis. 2017 Oct;22(10):1296-1309. doi: 10.1007/s10495-017-1399-6.