title: Neurotrophin-3 accelerates wound healing in diabetic mice by promoting a paracrine response in mesenchymal stem cells.
abstract: Angiogenesis is a major obstacle for wound healing in patients with diabetic foot wounds. Mesenchymal stem cells (MSCs) have an important function in wound repair, and neurotrophin-3 (NT-3) can promote nerve regeneration and angiogenesis. We investigated the effect of NT-3 on accelerating wound healing in the diabetic foot by improving human bone marrow MSC (hMSC) activation. In vitro, NT-3 significantly promoted VEGF, NGF, and BDNF secretion in hMSCs. NT-3 improved activation of the hMSC conditioned medium, promoted human umbilical vein endothelial cell (HUVEC) proliferation and migration, and significantly improved the closure rate of HUVEC scratches. In addition, we produced nanofiber mesh biological tissue materials through the electrospinning technique using polylactic acid, mixed silk, and collagen. The hMSCs stimulated by NT-3 were implanted into the material. Compared with the control group, the NT-3-stimulated hMSCs in the biological tissue material significantly promoted angiogenesis in the feet of diabetic C57BL/6J mice and accelerated diabetic foot wound healing. These results suggest that NT-3 significantly promotes hMSC secretion of VEGF, NGF, and other vasoactive factors and that it accelerates wound healing by inducing angiogenesis through improved activation of vascular endothelial cells. The hMSCs stimulated by NT-3 can produce materials that accelerate wound healing in the diabetic foot and other ischemic ulcers.
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.forename: Wen
authors.initials: W
authors.lastname: Zeng
authors.forename: Yang-Xiao
authors.initials: YX
authors.lastname: Wu
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Hou
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Ming-Can
authors.initials: MC
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Zhang
authors.forename: Chu-Hong
authors.initials: CH
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000628:therapy*; D017719:Diabetic Foot / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism; D020933:Neurotrophin 3 / Q000494:pharmacology*; D019899:Paracrine Communication / Q000187:drug effects*; D012038:Regeneration / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D020933:Neurotrophin 3; D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor