Department of Plastic Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road of Nanchang, Jiangxi, 330006, P. R. China.
Curr Pharm Biotechnol. 2022;23(6):894-901. doi: 10.2174/1389201022666210719154009.
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.
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.
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.
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.
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.
由于胶原沉积紊乱，糖尿病伤口的愈合情况较差。基质金属蛋白酶-9（MMP-9）与组织修复过程中的胶原沉积密切相关。许多研究表明，脂肪来源干细胞衍生的细胞外囊泡（ADSC-EVs）通过增强胶原沉积来促进糖尿病伤口愈合。
本研究旨在探讨 ADSC-EVs 是否通过改善胶原沉积来下调糖尿病伤口中 MMP-9 的表达，从而促进伤口愈合。我们在体外和体内测试了 ADSC-EVs 对 MMP-9 和糖尿病伤口愈合的潜在影响。
首先，我们使用 CCK-8、western blot 和 MMP-9 酶联免疫吸附试验（ELISA）评估了 ADSC-EVs 对 AGE-BSA 处理的 HaCaT 细胞增殖和 MMP-9 分泌的影响。接下来，通过 MMP-9 ELISA 和苏木精和伊红、Masson 三色、MMP-9 免疫荧光染色评估了 ADSC-EVs 在免疫缺陷小鼠模型中对糖尿病伤口液中愈合、再上皮化、胶原沉积和 MMP-9 浓度的影响。
在体外，ADSC-EVs 促进了 HaCaT 细胞的增殖和 MMP-9 的分泌。在体内，ADSC-EVs 通过改善再上皮化和胶原沉积以及抑制 MMP-9 的表达来加速糖尿病伤口的愈合。
ADSC-EVs 通过抑制 MMP-9 的下调和改善胶原沉积，具有在小鼠模型中治愈糖尿病伤口的潜力。因此，ADSC-EVs 是治疗糖尿病伤口的有前途的候选物。
