The role of adipose-derived stem cells-derived extracellular vesicles in the treatment of diabetic foot ulcer: Trends and prospects

Abstract

Diabetic foot ulcer(DFU) is one of the most severe chronic complications of type 2 diabetes mellitus, which is mainly caused by peripheral vascular occlusion with various degrees of infection. Treatment of DFU is difficult, and ulcer formation in lower limbs and deep-tissue necrosis might lead to disability or even death. Insulin resistance is the major mechanism of type 2 diabetes mellitus development, largely caused by adipose tissue dysfunction. However, adipose tissue was recently identified as an important endocrine organ that secretes bio-active factors, such as adipokines and extracellular vesicles(EVs). And adipose tissue-derived stem cells(ADSCs) are abundant in adipose tissue and have become a hot topic in the tissue engineering field. In particular, EVs derived from ADSCs contain abundant biomarkers and mediators. These EVs exert significant effects on distant cells and organs, contributing to metabolic homeostasis. In this review, we aim to elaborate on the mechanisms of diabetic non-healing wound development and the role of ADSCs-EVs in wound repair, which might provide a new therapy for treating DFU.

The Efficacy of Stem Cells in Wound Healing: A Systematic Review

“…Increasing evidence shows that exosomes derived from ADSCs exhibit anti-inflammatory properties through inducing the polarization of macrophages to the M2 type through the STAT-3 pathway and reducing inflammation. Exosomes contain microRNSAs, which reinforce the acceleration of wound healing [ 51 ]. Additionally, ADSC exosomes promote scarless wound healing by preventing fibroblasts from differentiating into myofibroblasts and resulting in better cosmesis.…”

Circ_072697 knockdown promotes advanced glycation end products-induced cell proliferation and migration in HaCaT cells via miR-3150a-3p/KDM2A axis

“…DFU wound healing is influenced by multiple factors, and its mechanisms mainly involve hyperglycemic-induced angiogenesis disorders, abnormal inflammatory response, and changes in the migration and proliferation of fibroblasts and keratin-forming cells. The pathological process of DFU is extremely complex and difficult to therapy [ 19 ]. Conventional treatments, such as glycemic control and interventional surgery, have certain limitations [ 20 ].…”

Stem Cell-Derived Extracellular Vesicles: Promising Therapeutic Opportunities for Diabetic Wound Healing

“… 20 In particular, ADSC-EVs are considered robust candidates for use in diabetic wound healing because of their potential functions of regulating cell proliferation and apoptosis and participating in angiogenesis, immunomodulation, and ECM remodeling. 21 It is worth noting that gene editing technology offers the possibility of amplifying the characteristic substances and functional synergies of cells. 22–25 …”