For instance, exosomes derived from hypoxia-preconditioned adipose-derived MSCs possess a higher capacity to enhance angiogenesis and promote graft survival compared with exosomes from untreated MSCs. Recently, studies have demonstrated that pretreated MSCs exhibit enhanced paracrine effects. Previous studies have reported that preconditioning of MSCs with various pretreatments, such as drugs, cytokines and physical factors is an effective approach to enhance the biological activities and function of MSCs in tissue regeneration. Based on these findings, exosomes may serve as a promising candidate to promote angiogenesis in wound healing. Therefore, exosomes are a cell-free therapeutic that may be safer than direct MSCs therapy and provide a potential modality for tissue regeneration. BMSCs-derived exosomes have been shown to stimulate the proliferation and osteogenic differentiation of BMSCs to promote new bone regeneration and neovascularization in bone defects. Recent research has reported that exosomes derived from MSCs have cardioprotective effects by inhibiting cardiomyocyte apoptotic injury. Compared with MSCs, exosomes possess advantageous properties, including good stability and low immunogenicity. Recent research identified that exosomes derived from BMSCs can significantly promote the neovascularization and regenerative capacity of promoting tissue repair.
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Many researchers have reported on the clinical use of bone marrow-derived MSCs in the treatment of diseases, including cardiac disease, pulmonary disease, and osteoarthritis. Bone marrow-derived MSCs (BMSCs) possess many advantages, including easier culturing, proliferation, isolation and purification, rendering them convenient for clinical application. Įxosomes, extracellular vesicles with a diameter between 30 and 150 nm, can transport proteins and growth factors to target cells where they exert different effects. An effective strategy that promotes wound angiogenesis can accelerate wound healing and has the potential to revolutionize the treatment of patients with diabetes.
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Accumulating evidence has supported that enhanced angiogenesis can improve the delivery of nutrients and oxygen to the wound sites, which can accelerate wound healing. Vascular dysfunction caused by hyperglycemia results in insufficient blood supply to the wound surface, and is an important underlying reason for diabetic wound healing failure. Current therapies include dressing changes and surgical debridement, but outcomes are not yet satisfactory. Diabetic wounds can have extensive negative repercussions on the quality of life of patients and result in great psychological distress. Graphic abstractĬomplications of diabetes, such as recalcitrant wounds, are a significant worldwide cause of disability and mortality. This offers a promising novel cell-free therapy for treating diabetic wound healing. PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis.
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LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing.
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Enhanced angiogenesis can promote diabetic wound healing.