LPS-pretreatment adipose-derived mesenchymal stromal cells promote wound healing in diabetic rats by improving angiogenesis

Mesenchymal stem cells (MSCs) play a key role in wound healing, and the advantages of pretreated MSCs in wound healing have previously been reported. In the present study, we investigated the impact of LPS pretreated human adipose-derived MSCs on skin wound healing in diabetic rats. We found that some improvements occurred through improving angiogenesis. Then, we scrutinized the impact of lipopolysaccharide (LPS) treatment on human adipose-derived MSCs in a high-glucose (HG) medium, as an in vitro diabetic model. In vivo findings revealed significant improvements in epithelialization and angiogenesis of diabetic wounds which received LPS pre-MSCs. Particularly, LPS pre-MSCs-treated diabetic wounds reached considerably higher percentages of wound closure. Also, the granulation tissue of these wounds had higher pronounced epithelialization and more vascularization compared with PBS-treated and MSCs-treated diabetic ones by CD31, VEGF, CD90, collagen 1, and collagen 3 immunostaining. Western-blots analyses indicated that LPS pre-MSCs led to the upregulation of vascular endothelial growth factor (VEGF) and DNMT1. In addition, significantly higher cell viability (proliferation/colonie), and elevated VEGF and DNMT1 protein expression were observed when MSCs were treated with LPS (10 ng/ml, 6 h) in HG culture media. Based on these findings, it is suggested that LPS pre-MSCs could promote wound repair and skin regeneration, in some major processes, via the improvement of cellular behaviors of MSCs in the diabetic microenvironment. The beneficial advantages of LPS treated with mesenchymal stem cells on wound healing may lead to establishing a novel approach as an alternative therapeutic procedure to cure chronic wounds in diabetic conditions.