Lysophosphatidic acid protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis

Jinghai Chen, A. R. Baydoun, Ruixia Xu, Linzi Deng, Xuebin Liu, Weiquan Zhu, Linhui Shi, Xiangfeng Cong, Shengshou Hu, Xi Chen

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84 Citations (Scopus)


Bone marrow-derived mesenchymal stem cells (MSCs) have shown great promise for cardiac repair. However, poor viability of transplanted MSCs within the ischemic heart has limited their therapeutic potential. Our previous studies have documented that hypoxia and serum deprivation (hypoxia/SD), induced MSCs apoptosis through the mitochondrial apoptotic pathway. Since serum lysophosphatidic acid (LPA) levels are known to be significantly elevated after acute myocardial infarction and that LPA enhanced survival of other cell systems, we embarked on determining whether LPA protects MSCs against hypoxia/SD-induced apoptosis. We have also investigated the potential mechanism(s) that may mediate such actions of LPA. All experiments were carried out on rat bone marrow MSCs. Apoptosis was induced by exposure of cells to hypoxia/SD in a sealed GENbox hypoxic chamber. Effects of LPA were investigated in the absence and presence of inhibitors that target either G(i)proteins, the mitogen activated protein kinases ERK1/2, or phosphoinositide 3-kinase (PI3K). The data obtained showed that hypoxia/SD-induced apoptosis was significantly attenuated by LPA through Gi-coupled LPA(1) receptors linked to the downstream ERK1/2 and PI3K/Akt signaling pathways that function in parallel. Additional studies have demonstrated that hypoxia/SD-induced activation of mitochondrial dysfunction was virtually abolished by LPA treatment and that inhibition of the LPA(1) receptor, Gi proteins, the PI3K/Akt pathway, or ERKs effectively reversed this protective action of LPA. Taken together, our findings indicate that LPA is a novel, potent survival factor for MSCs and this may prove to be of considerable therapeutic significance in terms of exploiting MSC-based therapy in the infracted myocardium.
Original languageEnglish
Pages (from-to)135-45
Number of pages11
JournalStem Cells
Issue number1
Publication statusPublished - Jan 2008


  • Animals
  • Apoptosis
  • Blotting, Western
  • Caspase 3
  • Cell Hypoxia
  • Cell Survival
  • Cells, Cultured
  • Extracellular Signal-Regulated MAP Kinases
  • Flow Cytometry
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Lysophospholipids
  • Membrane Potential, Mitochondrial
  • Mesenchymal Stem Cells
  • Phosphatidylinositol 3-Kinases
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serum
  • Signal Transduction


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