Fig. 5
Counteraction of AMPK attenuated metformin-induced MSC apoptosis in vivo. a Diabetic mice were administered with PBS, metformin (250 mg/kg/day, i.g.), or metformin + compound C (0.1 mg/kg/day, i.g.) by gavage for 4 weeks, and then all mice were sacrificed to isolate mBMSCs for flow cytometry assay. b Metformin treatment induced a significant decrease in mBMSCs compared with PBS treatment. Compared with metformin, compound C reduced the metformin-induced mBMSC decrease (CD45−/CD105+/CD90+/Sca-1+). *p < 0.01 vs. PBS, #p < 0.01 vs. Met, by one-way ANOVA, n = 5 per group. c Post-MI hearts with CM-DiI-labeled MSC transplantation were enzymatically digested, and small cells from the heart (< 30 μm diameter) were collected after the depletion of cardiomyocytes. As indicated with a yellow arrow, CM-DiI-labeled cells represent surviving MSCs under fluorescence microscopy. Scale bar = 100 μm. d Representative flow cytometric plots of surviving CM-DiI+ MSCs counted by FCM. Gate R4 indicates the CM-DiI+ cells out of all the isolated cells from the heart. e The percentage of surviving MSCs out of the total transplanted MSCs at different time points. *p < 0.05 vs. MSCs, #p < 0.05 vs. MSCs + Met, by one-way ANOVA, n = 15 per time points. f, g Comparison among human peripheral blood MSCs (CD34−/CD11b−/CD19−/CD45−/HLA-DR−/CD90+/CD73+/CD105+) from healthy controls (control, n = 10), diabetic patients without metformin medication history (T2DM, n = 10), and diabetic patients with metformin medication history (T2DM-M, n = 10). Symbols represent individual subjects; horizontal lines show the mean; and data are presented as the means ± SD, statistical test applied by one-way ANOVA. Met metformin, C compound C, T2DM type 2 diabetes mellitus, mBMSC mouse bone marrow mesenchymal stromal cell