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Resent study suggests that c-kit + cells in bone marrow-derived MSCs may differentiate toward cardiamyocytes. However, the properties of c-kit + MSCs remain unclear. This study isolated c-kit + VEGFR-2 + cells from rat bone marrow-derived MSCs, and assessed potential of c-kit + VEGFR-2 + MSCs to differentiate towards cardiovascular cells and their efficiency of repairing the infarcted myocardium after transplantation. Gene expression profile of the cells was analyzed with RNA-sequencing. Potential of differentiation of the cells was determined after induction. Rat models of myocardial infarction were established by ligation of the left anterior descending coronary artery. The cells were treated with hypoxia and serum deprivation for four hours before transplantation. Improvement of cardiac function and repair of the infarcted myocardium were assessed at four weeks after transplantation. Gene expression profile revealed that c-kit + VEGFR-2 + MSCs expressed most smooth muscle-specific and myocardium-specific genes, while expression of endothelium-specific genes was upregulated significantly. After induction with VEGF or TGF-β for two weeks, the cells expressed CD31 and α-SMA respectively. At three weeks, BMP-2-induced cells expressed cTnT. After transplantation of the cells, cardiac function was improved, scar size of the infarcted myocardium was decreased, and angiogenesis and myocardial regeneration were enhanced significantly. Moreover, paracrine in the myocardium was increased after transplantation. These results suggest that c-kit + VEGFR-2 + MSCs have a potential of differentiation towards cardiovascular cells. Transplantation of c-kit + VEGFR-2 + MSCs is effective for repair of the infarcted myocardium. c-kit + VEGFR-2 + MSCs may be a reliable source for cell therapy of ischaemic diseases., (© 2022. The Author(s).)

Stem cell transplantation has been limited by poor survival of the engrafted cells in hostile microenvironment of the infarcted myocardium. This study investigated cytoprotective effect of rapamycin-preactivated autophagy on survival of the transplanted mesemchymal stem cells (MSCs). MSCs isolated from rat bone marrow were treated with 50 nmol/L rapamycin for 2 h, and then the cytoprotective effect of rapamycin was examined. After intramyocardial transplantation in rat ischemia/reperfusion models, the survival and differentiation of the rapamycin-pretreated calls were accessed. After treatment with rapamycin, autophagic activities and lysososme production of the cells were increased significantly. In the condition of short-term or long-term hypoxia and serum deprivation, the apoptotic cells in rapamycin-pretreated cells were less, and secretion of HGF, IGF-1, SCF, SDF-1 and VEGF was increased. After transplantation of rapamycin-pretreated cells, repair of the infarcted myocardium and restoration of cardial function were enhanced dramatically. Expression of HGF, IGF-1, SCF, SDF-1, VEGF, HIF-1α and IL-10 in the myocardium was upregulated, while expression of IL-1β and TNF-α was downregulated. Tracing of GFP and Sry gene showed that the survival of rapamycin-pretreated cells was increased. Cardiomyogenesis and angiogenesis in the infarcted myocardium were strengthened. Some rapamycin-pretreated cells differentiated into cardiomyocytes or endothelial cells. These results demonstrate that moderate preactivation of autophagy with rapamycin enhances the survival and differentiation of the transplanted MSCs. Rapamycin-primed MSCs can promote repair of the infarcted myocardium and improvement of cardiac function effectively.

Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF-1α, Tβ4, VEGF and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF-1α, Tβ4, VEGF, SDF-1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial-derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c-kit + cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c-kit + cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Resent study suggests that c-kit+ cells in bone marrow-derived MSCs may differentiate toward cardiamyocytes. However, the properties of c-kit+ MSCs remain unclear. This study isolated c-kit+VEGFR-2+ cells from rat bone marrow-derived MSCs, and assessed potential of c-kit+VEGFR-2+ MSCs to differentiate towards cardiovascular cells and their efficiency of repairing the infarcted myocardium after transplantation. Gene expression profile of the cells was analyzed with RNA-sequencing. Potential of differentiation of the cells was determined after induction. Rat models of myocardial infarction were established by ligation of the left anterior descending coronary artery. The cells were treated with hypoxia and serum deprivation for four hours before transplantation. Improvement of cardiac function and repair of the infarcted myocardium were assessed at four weeks after transplantation. Gene expression profile revealed that c-kit+VEGFR-2+ MSCs expressed most smooth muscle-specific and myocardium-specific genes, while expression of endothelium-specific genes was upregulated significantly. After induction with VEGF or TGF-β for two weeks, the cells expressed CD31 and α-SMA respectively. At three weeks, BMP-2-induced cells expressed cTnT. After transplantation of the cells, cardiac function was improved, scar size of the infarcted myocardium was decreased, and angiogenesis and myocardial regeneration were enhanced significantly. Moreover, paracrine in the myocardium was increased after transplantation. These results suggest that c-kit+VEGFR-2+ MSCs have a potential of differentiation towards cardiovascular cells. Transplantation of c-kit+VEGFR-2+ MSCs is effective for repair of the infarcted myocardium. c-kit+VEGFR-2+ MSCs may be a reliable source for cell therapy of ischaemic diseases. [ABSTRACT FROM AUTHOR]