Abstract 237: Pharmacological Preconditioning Enhances Survival of Transplanted Mesenchymal Stem Cells in the Ischemic Myocardium.
Background: Poor cell viability of mesenchymal stem cells (MSCs) after transplantation has limited their reparative capability . Preconditioning (PC) plays a pivotal role in protection of ischemic myocardium. We hypothesized that PC enhances the protective effects of MSCs in repair of ischemic myocardium via PC signaling pathways.
Methods: Animals were grouped (n = 6) after LAD ligation in rats for 4 weeks to receive the intramyocardial injection of 20μl DMEM without cells, or with 5 ×105 MSCs without PC (group1), or 5 ×105 PC MSCs with BMS, a mitoKATP channel agonist (6μmol/l; group 2), and with 5×105 PC MSCs with BMS and 5HD(6μmol/l,100μmol/l respectively, group 3). All transplanted cells were labeled with PKH26.One month later echocardiography was done and transplanted hearts were harvested for histological and phenotypic analysis of transplanted cells using c-Kit, CD31, PKH26 labeled cells as markers of origin of transplanted cells.LV fibrosis was measured with Masson Trichrome staining . TUNEL was used to assess the degree of apoptosis.
Results: Extensive regeneration and survival of MSCs was observed in and around the infarcted myocardium in group 2 (see table⇓). Blood vessel density as shown by incorporation of CD31 positive cells was markedly enhanced in group 2 as compared with group1. Fibrosis was significantly reduced resulting in improved heart function in group 2. Protection of PC was significantly reduced by 5-HD (p< 0.05). PCR analysis showed CXCR4 upregulation in PC group 2, and 5-HD abolished this overexpression. Apoptosis was also reduced in group 2.
Conclusion: PC upregulated CXCR4 expression in transplanted MSCs, which rendered them more resistant to ischemic environment.PC enhanced MSCs survival, reduced apoptosis and increased engraftment of transplanted cells . P-value < 0.05 vs group 1, was considered significant; PKH26, cardiomyocytes labeled with PKH26; P,positive ;HPF, high power field; % of LV, percentage of left ventricle.