Production and Biological Effects of Extracellular Vesicles from Adipose-Derived Stem Cells Were Markedly Increased by Low-Intensity Ultrasound Stimulation for Promoting Diabetic Wound Healing

• Published in: Stem cell reviews and reports Vol. 19; no. 3; pp. 784 - 806
• Main Authors: Zheng, Yi, Xu, Peng, Pan, Chuqiao, Wang, Yikai, Liu, Zibo, Chen, Yahong, Chen, Chuhsin, Fu, Shibo, Xue, Ke, Zhou, Qimin, Liu, Kai
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2023; Springer Nature B.V
• Subjects: Adipose Tissue; Angiogenesis; Animals; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Cell Biology; Cell differentiation; Cell proliferation; Collagen; Diabetes; Diabetes Mellitus; Endothelial Cells; Extracellular Vesicles; Fibroblasts; Keratinocytes; Life Sciences; Mice; Nanoparticles; Regenerative Medicine/Tissue Engineering; Secretion; Stem Cells; Ultrasonic imaging; Ultrasound; Wound healing; Wound Healing - physiology; United States > US; Low-intensity ultrasound stimulation; Extracellular vesicles; Adipose-derived stem cells; Cell-derived nanoparticles; Diabetic wound healing
• ISSN: 2629-3269; 2629-3277
• DOI: 10.1007/s12015-022-10487-w

Diabetic wound treatment has posed a significant challenge in clinical practice. As a kind of cell-derived nanoparticles, extracellular vesicles produced by adipose-derived stem cells (ADSC-EVs) have been reported to be potential agents for diabetic wound treatment. However, ADSC-EV yield is insufficient to meet the demands of clinical therapy. In this study, a novel method involving the use of low-intensity ultrasound stimulation on ADSCs is developed to promote EV secretion for clinical use. A proper low-intensity ultrasound stimulation parameter which significantly increases ADSC-EV quantity has been found. In addition, EVs secreted by ADSCs following low-intensity ultrasound stimulation (US-EVs) are enriched in wound healing-related miRNAs. Moreover, US-EVs promote the biological functions of fibroblasts, keratinocytes, and endothelial cells in vitro, and promote diabetic wound healing in db/db mice in vivo through re-epithelialization, collagen production, cell proliferation, keratinocyte differentiation and migration, and angiogenesis. This study proposes low-intensity ultrasound stimulation as a new method for promoting significant EV secretion by ADSCs and for improving the diabetic wound-healing potential of EVs, which will meet the clinical needs for these nanoparticles. Graphical Abstract The production of extracellular vesicles of adipose-derived stem cells is obviously promoted by a low-intensity ultrasound stimulation method, and the biological effects of promoting diabetic wound healing were markedly increased in vitro and in vivo