Neural stem cells promote angiogenesis to accelerate diabetic wound healing through the paracrine pathway
YOU Shuang
DANG Juanli
YU Zhou
SONG Baoqiang
Abstract：Objective To investigate the promoting effect of neural stem cells(NSCs)on diabetic wound healing and to elucidate the underlying mechanisms involved in regulating angiogenesis.Methods NSCs were aseptically isolated from embryonic day 14.5 C57BL/6 mouse embryos and identified by immunofluorescence staining for stemness markers.The effects of NSCs-conditioned medium(NSCs-CM)on the proliferation,migration,and tube formation ability of human umbilical vein endothelial cells(HUVECs)were assessed using CCK-8 assay,Transwell assay,and Matrigel tube formation assay.A full-thickness skin defect model was established in diabetic mice induced by a high-fat diet combined with streptozotocin.The model mice were randomly divided into a control group and an NSC-treated group,receiving local injections of PBS or NSCs suspension around the wound edges,respectively.Wound closure rates were dynamically monitored.Tissue repair and neovascularization were evaluated by HE staining and CD31 immunohistochemical staining.The mRNA expression levels of angiogenesis-related factors in the wound tissue were detected by qRT-PCR.Results NSCs highly expressing SOX2 and Nestin were successfully isolated and cultured.In vitro experiments showed that NSCs-CM significantly promoted the proliferation,migration,and tube formation of HUVECs.In vivo results demonstrated that compared with the control group,local NSCs transplantation significantly accelerated the wound healing rate in diabetic mice,increased the thickness of the regenerated epidermis and the density of new blood vessels in the wound,and markedly upregulated the mRNA expression levels of vascular endothelial growth factor-A,vascular endothelial growth factor receptor 2,angiopoietin-1,and angiopoietin-2 in the wound tissue(P<0.01).Conclusion NSCs can upregulate the expression of pro-angiogenic factors,enhance the functional activity of vascular endothelial cells through a paracrine mechanism,promote wound neovascularization,and thereby accelerate diabetic wound healing.This study provides new experimental evidence for the application of NSCs in the treatment of diabetic wounds.
Keywords：neural stem cellsdiabetes mellitusparacrinewound healingangiogenesisvascular endothelial cellscell proliferationcell migration
Publication Date：2026-05-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：8( 714-721 )