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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Extracellular Vesicles Derived from Adipose-Derived Stem Cells Accelerate Diabetic Wound Healing by Suppressing the Expression of Matrix Metalloproteinase-9

Author(s): Jiang-wen Wang, Yuan-zheng Zhu, Xuan Hu, Jia-ying Nie, Zhao-hui Wang, Shu Wu* and Yang-yan Yi*

Volume 23, Issue 6, 2022

Published on: 19 July, 2021

Page: [894 - 901] Pages: 8

DOI: 10.2174/1389201022666210719154009

Price: $65

Abstract

Background: The healing of diabetic wounds is poor due to a collagen deposition disorder. Matrix metalloproteinase-9 (MMP-9) is closely related to collagen deposition in the process of tissue repair. Many studies have demonstrated that extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) promote diabetic wound healing by enhancing collagen deposition.

Objective: In this study, we explored whether ADSC-EVs could downregulate the expression of MMP-9 in diabetic wounds and promote wound healing by improving collagen deposition. The potential effects of ADSC-EVs on MMP-9 and diabetic wound healing were tested both in vitro and in vivo.

Methods: We first evaluated the effect of ADSC-EVs on the proliferation and MMP-9 secretion of HaCaT cells treated with advanced glycation end product-bovine serum albumin (AGE-BSA) using CCK-8, western blot and MMP-9 enzyme-linked immunosorbent assay(ELISA). Next, the effects of ADSC-EVs on healing, re-epithelialisation, collagen deposition, and MMP-9 concentration in diabetic wound fluids were evaluated in an immunodeficient mouse model via MMP-9 ELISA and haematoxylin and eosin, Masson’s trichrome, and immunofluorescence staining for MMP-9.

Results: In vitro, ADSC-EVs promoted the proliferation and MMP-9 secretion of HaCaT cells. In vivo, ADSC-EVs accelerated diabetic wound healing by improving re-epithelialisation and collagen deposition and by inhibiting the expression of MMP-9.

Conclusion: ADSC-EVs possess the potential of healing of diabetic wounds in a mouse model by inhibiting downregulating MMP-9 and improving collagen deposition. Thus, ADSC-EVs are a promising candidate for the treatment of diabetic wounds.

Keywords: Wound healing, diabetic wounds, adipose-derived stem cells, extracellular vesicles, matrix metalloproteinase-9, collagen deposition.

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