Abstract
The therapeutic potential of adipose-derived stem cell conditioned medium (ASC-CM) was studied in the rabbit model of critical limb ischemia (CLI). Rabbits received treatment with ASC-CM or placebo. Gastrocnemius muscle tissue was collected 35 days after ischemia induction. Ischemic changes were evaluated in hematoxylin-eosin stained tissues for early (necrotic lesions/granulation tissue) and late (fibrous scars) phases of tissue repair. The expression of proangiogenic miR-126 was also evaluated using in situ hybridization. The levels of cytokines, insulin, and C-peptide were measured in blood. Early repair phases were observed more often in placebo-treated samples (45.5%) than in ASC-CM-treated ones (22.2%). However, the difference was not statistically significant. We demonstrated a statistically significant positive correlation between the early healing phases in tissue samples and C-peptide levels in peripheral blood. The expression of proangiogenic miR-126 was also shown in a number of structures in all phases of ischemic tissue healing. Based on our results, we believe that treatment with ASC-CM has the potential to accelerate the healing process in ischemic tissues in the rabbit model of CLI. The whole healing process was accompanied by miR-126 tissue expression. C-peptide could be used to monitor the course of the tissue healing process.
Highlights
Wound healing is a complex series of events that occur through the intricately coordinated actions and timing of many different processes
In our previous study[8], we demonstrated in the rabbit model of critical limb ischemia that adipose-derived stem cell-conditioned medium (ASC-CM) can accelerate neovascularization and significantly improve ischemic tissue reperfusion
This study addresses the relationship between ASCCM treatment, diabetes induced in rabbits, serum levels of selected proteins and the rate of healing of ischemic muscle tissue
Summary
Wound healing is a complex series of events that occur through the intricately coordinated actions and timing of many different processes. Wound healing is categorized into four sequential and overlapping phases: (1) haemostasis; (2) inflammation; (3) proliferation; and (4) remodelling. Following injury, the haemostasis phase begins with vascular constriction, platelet aggregation, and clot formation. This leads to the inflammation phases in which immune and inflammatory cells are recruited to the wound bed and bacteria are cleared. Overlapping the inflammation phase is the proliferation phase. Vascular disease, and trauma are the main factors leading to the development of DFU, impaired wound healing is the main issue leading to the development of chronic wounds and lower extremity amputations[7]
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