Preconditioning by lysophosphatidic acid enhancing early survival of implanted mesenchymal stem cells following myocardial infarction

Hou Jian-feng; Liu Xue-bin; Cong Xiang-feng; Hu Sheng-shou; Chen Xi

doi:10.13498/j.cnki.chin.j.ecc.2015.01.17

Abstract：Objective To evaluate the effects of lysophosphatidic acid ( LPA) preconditioning on early survival of implanted mesenchymal stem cell ( MSCs) in rat models of myocardial infarction ( MI) . Methods Male SD rat MSCs were prepared and subjec?ted to hypoxia and serum deprivation. The secretion of vascular endothelial growth factor ( VEGF) from MSCs were evaluated by ELISA. MI model was induced by left coronary artery ligation in female SD rats. Three weeks later, the qualified animals were allocated ran?domly to 3 groups, 1.DMEM group:to receive intramyocardial injection with 30μl DMEM, 2.MSCs group:to receive intramyocardial injection with 2×106 male rat MSCs, and 3. L-MSCs group:to receive intramyocardial injection with 2×106 LPA-preconditioning male MSCs. Cell survival was assayed with quantitative real-time polymerase chain reaction to identify Y chromosome gene and apoptosis was assayed with TUNEL staining. Capillary density was estimated by the immunohistochemistry. The echocardiogram ( UCG) was used to evaluate the heart function. Results LPA (10 μM) enhanced VEGF release from MSCs under hypoxia/SD in vitro . Compared with MSCs group and DMEM group, although there was no difference in the improved heart function, LPA preconditioning significantly en?hanced early cell survival rate by nearly 2-fold(1 hour:50.93±11.43% vs. 23.63±2.24%, P =0.28;1 day:34.96±12.1% vs. 14.75 ±1%, P =0.31;1 week:1.38±0.35% vs. 0.69±0.14%, P =0.44), and decreased the apoptotic percentage of implanted MSCs in in?farcted myocardium thus increased the number of newly formed capillaries. Conclusion LPA preconditioning could be a novel ap?proach for cell transplantation to enhance the early cell survival and the therapeutic potential.