Figure 2.

iPan-injection of MSC CdM maintained beta cell mass in CK19-CreERT Rosa26-mTomato mice using a 21-day Protocol. (A) Tamoxifen- (6 mg/day, day −7, −6) and STZ-injected (50 mg/kg/day, days 0-4) CK19-CreERT Rosa26-mTomato female and male mice that were hyperglycemic (> 12 mmol/L) on day 10 were iPan-injected with unconditioned basal media, Wnt+ CdM, or Untreated CdM and non-fasted blood glucose was monitored for 21 days. (B) Blood glucose levels at days 17 and 21 were lower in mice administered Wnt+ CdM (n = 15) or Untreated CdM (n = 16) compared to mice administered unconditioned basal media (n = 12). Dotted line represents glycemia levels in control mice injected with citric acid buffer instead of STZ (no STZ, n = 6). (C) Areas under the blood glucose curves were similar between treatment groups. (D,E) Beta cell mass and insulin + islet number/mm² were increased at day 21 in mice administered Wnt+ CdM or Untreated CdM compared to mice administered unconditioned basal media. (F) Representative images of insulin staining in pancreas sections from mice administered unconditioned basal media, Wnt+ CdM, Untreated CdM, or no STZ control. Scale bars = 150 µm. (G) Beta cell/alpha cell area was increased in mice administered Wnt+ CdM or Untreated CdM compared to mice administered unconditioned basal media. (H) Representative images of insulin+ and glucagon+ cells in islets from mice administered Wnt+ CdM, Untreated CdM, or unconditioned basal media. Scale bars = 20 μm. (I) Representative flow cytometry plots of insulin+ cells that co-expressed tdTomato in mice iPan-injected with unconditioned basal media, Wnt+ CdM, or Untreated CdM. (J) At day 21, the frequency of insulin+/tdTomato+ cells was increased in mice that received Wnt+ CdM compared to mice that received unconditioned basal media. Data is shown as mean ± SD (*P < 0.05; *P < 0.01; ***P < 0.001) using matched CdM from a total of N = 8 human MSC samples.