Fig. 4. Engineered therapeutic factor-secreting hBM-MSCs improved kinetics of wound healing in acute diabetic wounds.
a Excisional stented wounds created on the dorsal skin of hyperglycemic (>500 mg/dl blood glucose) db/db mice were treated with 2.5 × 105 engineered therapeutic factor-secreting hBM-MSCs and imaged with digital photography every other day until complete closure. Relative wound size were determined by measuring the wound area relative to constant silicone ring area, and normalized to original wound size. Areas under the curve (AUC) were calculated for each individual wound. Time to complete closure was determined in 2-day intervals and unclosed wounds were excluded at the end of observation periods. b Bars represent average (n = 2 technical cell-plating replicates for all groups except PDGFB MSCs (n = 3 technical cell-plating replicates)) total level of therapeutic proteins secreted by 2.5 × 105 engineered hMSCs, wild-type, and GFP-integrated controls over 24 h, as quantified by ELISA assay. c Dots and lines show changes in average relative wound size over time of engineered hBM-MSC treatments against PBS vehicle-treated and baseline MSC controls (biological replicate: n = 10 wounds per treatment group). Error bars represent standard error of mean. Daggers represent same control datasets. d Box and whiskers plots show AUC of individual wounds (n = 10 per treatment group), which were normalized against mean AUC of PBS controls (n = 10 PBS control wounds) within the same experimental runs. Minima and maxima are bounded by whiskers. Box lower bounds, centers, and upper bounds represent the 25th, 50th, and 75th percentiles, respectively. Mean AUCs of all treatment groups were different according to ordinary one-way ANOVA test (p < 0.0001). Mean AUCs of engineered hBM-MSCs treated wounds were compared to that of control hBM-MSCs-treated wounds using Dunnett’s test. Reported p-values were corrected for multiple comparison. Asterisks indicate level of significance (**p < 0.01; ****p < 0.0001). e Kaplan–Meier’s plots represent time to complete wound closure of engineered hBM-MSCs treated wounds, as compared to control hBM-MSC treatment. Chi-square p-values represent significant difference in time to closure between two groups according to Log-rank test. Daggers represent same control datasets. Source data are available in the Source data file.