| Popis: |
Background: Poor viability of transplanted mesenchymal stem cells (MSCs)within the ischemic heart has limited their therapeutic potential for cardiac repair. We have recently demonstrated that adiponectin (APN) inhibits the apoptosis of MSCs under hypoxia and serum-deprivation conditionsin vitro. This study investigated whether APN could promote the survival of MSCs in vivoand further contribute to cardiac repair after acute myocardial infarction (AMI), via the adenosine monophosphate-activated protein kinase(AMPK)pathway. Methods: Rats were randomized into six groups: the Sham, AMI control, and 4 other groups that were subjected to AMI followed by treatment with MSCs, APN, APN + MSCs and APN + MSCs + AMPK inhibitor. MSCs labeled with CM-Dil were injected through the jugular vein in 24 hours post AMI. At 4-week after AMI, engraftment of MSCs to the peri-infarct myocardium was evaluated. Cardiac function was assessed using echocardiography and left heart catheterization. Apoptosis and fibrosis were measured with TUNEL and Masson’s trichrome staining. H&E staining and immunohistochemistry against CD 68 and CD 206 were performed to assess the infiltration of inflammatory cells. Expressions of inflammatory cytokines were determined with ELISA. Immunostaining against smooth muscle cell marker α-smooth-muscle actin (α-SMA) and endothelial cell marker CD31 antibodies were performed to assess arteriogenesis and angiogenesis. Results: APN treatment significantly enhanced the engraftment and survival rate of transplanted MSCs accompanied by markedly improved cardiac function and decreased infarct size at 4-week after AMI. Combined administration of APN and MSCs markedly suppressed inflammatory response, specifically promoted shift of infiltrated macrophages to anti-inflammatory phenotype.Combined administration of APN and MSCs also significantly inhibited cardiomyocytes apoptosis, while increased arteriogenesis and angiogenesis in the peri-infarct myocardium when compared with MSCs transplantation alone. These protective effects of APN were associated with AMPK phosphorylation, which were almost completely reversed by AMPK pathway inhibitor. Conclusions: Our results demonstrated that APN could improve the survival and therapeutic efficacy of transplanted MSCs after AMI through AMPK activation.Our study suggests the potential application of APN for improvement of stem cell-based heart repair and regeneration. |
