Abstract

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.

Details

Title
Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model
Author
Li, Xue 1 ; Xie, Xiaoyun 1 ; Lian, Weishuai 1 ; Shi, Rongfeng 1 ; Han, Shilong 1 ; Zhang, Haijun 2 ; Lu, Ligong 3 ; Li, Maoquan 1   VIAFID ORCID Logo 

1  Department of Interventional & Vascular Surgery, Tenth People’s Hospital of Tongji University, Shanghai, China; Institute of Interventional & Vascular Surgery, Tongji University, Shanghai, China 
2  Institute of Interventional & Vascular Surgery, Tongji University, Shanghai, China; National United Engineering Laboratory for Biomedical Material Modification, Branden Biomedical Park, Qihe Advanced Science & High Technology Development Zone, Qihe, Shandong, China 
3  Institute of Interventional & Vascular Surgery, Tongji University, Shanghai, China; Zhuhai people’s hospital, Zhuhai City, China 
Pages
1-14
Publication year
2018
Publication date
Apr 2018
Publisher
Springer Nature B.V.
ISSN
12263613
e-ISSN
20926413
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s12276-018-0058-5
ProQuest document ID
2036806724
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.