Journal
CELL TRANSPLANTATION
Volume 22, Issue 6, Pages 1011-1021Publisher
SAGE PUBLICATIONS INC
DOI: 10.3727/096368912X657495
Keywords
Neurotrophin-3 (NT-3); Mesenchymal stem cells (MSCs); Diabetic foot; Paracrine; Vascular
Funding
- Joint Research Fund for Overseas Chinese Young Scholars [310 28008]
- Natural Science Foundation Project of CQ CSTC [cstc 2011jjjq0016]
- twelve-five key project of PLA [BWS11C 056]
- National Science Foundation of China [3117 0935]
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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.
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