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

Abstract

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 CGday4 and CGday8 groups served as controls. In the AGday4 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 reduced microbiological counts compared to the control group on days 4 and 8. Moreover, in the AGday8 group compared to the AGday4 group, this decline in microbiological counts was even more pronounced. Moreover, we observed that the stereological characteristics in the AGday4 and AGday8 groups were significantly superior to those in the CG groups. Additionally, the AGday4 and AGday8 groups exhibited smaller ulcer area sizes compared to the CG groups. Furthermore, the AGday4 and AGday8 groups demonstrated higher expression levels of FGF2 and microRNA-21 than the CG groups on days 4 and 8. Notably, on day 8, the AGday8 group’s outcomes surpassed those of the AGday4 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.