Adipose-derived Stem Cells Improving Inflammatory and Proliferative Responses in an Infected and Ischemic Ulcer Model in Type 1 Diabetic Rats: Insights Into Bacterial Count, Stereological Parameters, microRNA-21, and FGF2 Regulation

Background: Adipose-derived stem cells (ADSCs) have been shown to enhance wound healing in rats with type 1 diabetes (DM1). Objectives: This experimental study aimed to explore how ADSC administration affects bacterial count, wound size, biomechanical and stereological parameters, and the expression of microRNA-21 and FGF2 in a rat model of infected, ischemic, and delayed wound healing in DM1. Methods: Twenty-four male adult Wistar rats weighing less than 250 g were randomly assigned to four groups (n = 6 per group). Type 1 diabetes was induced in all animals, resulting in the development of a delayed, ischemic, and infected wound model. The CG(day4) and CG(day8) groups served as controls. In the AG(day4) group, the animals received allograft h-ADSs and were euthanized on day four after surgery. Similarly, in the AGday8 group, the animals received h-ADSs and were euthanized on day eight after surgery. Microbial colony counts, wound size, stereological parameters, and the expression of microRNA-21 and FGF2 were evaluated in this study during the inflammation (day 4) and proliferation (day 8) stages of wound healing. Results: We demonstrated that h-ADSs significantly reducedmicrobiological counts compared to the control group on days 4 and 8. Moreover, in the AG(day8) group compared to the AG(day4) group, this decline in microbiological counts was even more pronounced. Moreover, we observed that the stereological characteristics in the AG(day4) and AG(day8) groups were significantly superior to those in the CG groups. Additionally, the AG(day4) and AG(day8) groups exhibited smaller ulcer area sizes compared to the CG groups. Furthermore, the AG(day4) and AG(day8) groups demonstrated higher expression levels of FGF2 and microRNA-21 than the CG groups on days 4 and 8. Notably, on day 8, the AG(day8) group's outcomes surpassed those of the AG(day4) group (P < 0.01). Conclusions: Through lowering microbial counts, modifying stereological parameters, microRNA-21, and FGF2 expression, the administration of hADS dramatically speeds up the healing of MARS-infected and ischemic ulcers in DM1 rats.