Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model

• Published in: Experimental & molecular medicine 2018, 50(0), , pp.1-14
• Main Authors: Li, Xue, Xie, Xiaoyun, Lian, Weishuai, Shi, Rongfeng, Han, Shilong, Zhang, Haijun, Lu, Ligong, Li, Maoquan
• Format: Article
• Language: English
• Subjects: 13; 13/2; 13/21; 13/31; 38/77; 631/532/1360; 631/80/86/2366; 82/51; 96/100; 96/31; Adipose Tissue - cytology; Adult; Aged; Amputation; Angiogenesis; Animals; Biomarkers; Biomedical and Life Sciences; Biomedicine; Blood Glucose; Case-Control Studies; Cellular Senescence; Cytokines - metabolism; Data processing; Diabetes; Diabetes mellitus; Diabetic Foot - genetics; Diabetic Foot - metabolism; Diabetic Foot - pathology; Disease Models, Animal; Endothelial Progenitor Cells - cytology; Endothelial Progenitor Cells - metabolism; Exosomes; Exosomes - metabolism; Feet; Female; Foot diseases; Gene Expression; Glucose; Humans; Inflammation Mediators - metabolism; Leg ulcers; Male; Medical Biochemistry; Middle Aged; Molecular Medicine; Neovascularization, Pathologic; Neovascularization, Physiologic - genetics; NF-E2-Related Factor 2 - genetics; Oxidative Stress; Patients; Progenitor cells; Rats; Senescence; Stem cell transplantation; Stem Cells; Stem Cells - cytology; Stem Cells - metabolism; Ulcers; Vascularization; Wound healing; Wound Healing - genetics; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-018-0058-5

Diabetic foot ulcers (DFU) increase the risks of infection and amputation in patients with diabetes mellitus (DM). The impaired function and senescence of endothelial progenitor cells (EPCs) and high glucose-induced ROS likely exacerbate DFUs. We assessed EPCs in 60 patients with DM in a hospital or primary care setting. We also evaluated the therapeutic effects of exosomes secreted from adipose-derived stem cells (ADSCs) on stress-mediated senescence of EPCs induced by high glucose. Additionally, the effects of exosomes and Nrf2 overexpression in ADSCs were investigated in vitro and in vivo in a diabetic rat model. We found that ADSCs that secreted exosomes promoted proliferation and angiopoiesis in EPCs in a high glucose environment and that overexpression of Nrf2 increased this protective effect. Wounds in the feet of diabetic rats had a significantly reduced ulcerated area when treated with exosomes from ADSCs overexpressing Nrf2. Increased granulation tissue formation, angiogenesis, and levels of growth factor expression as well as reduced levels of inflammation and oxidative stress-related proteins were detected in wound beds. Our data suggest that exosomes from ADSCs can potentially promote wound healing, particularly when overexpressing Nrf2 and therefore that the transplantation of exosomes may be suitable for clinical application in the treatment of DFUs. Diabetes: Rescue sacs for foot ulcers Tiny membrane-bound sacs released by some stem cells carry chemicals that can heal the foot ulcers that are a major complication of diabetes. The sacs, called exosomes, are released by many cells for signaling between cells and other functions. Xue Li of Tongji University in Shanghai and co-workers focused on the effects of exosomes from stem cells derived from body fat cells. They found that the exosomes could encourage the healing of diabetic foot ulcers in rats. The research also uncovered useful information about the molecular interactions involved in the accelerated healing. It revealed the significance of one particular protein in the formation of new blood vessels, which is central to the healing. The authors suggest that collecting and transplanting suitable exosomes could offer a new approach for treating diabetic foot ulcers.