Neurotrophin-3 Accelerates Wound Healing in Diabetic Mice by Promoting a Paracrine Response in Mesenchymal Stem Cells
Neurotrophin-3 Accelerates Wound Healing in Diabetic Mice by Promoting a Paracrine Response in Mesenchymal Stem Cells
复制标题
Neurotropin-3 通过促进间充质干细胞的旁分泌反应来加速糖尿病小鼠的伤口愈合
DOI：
10.3727/096368912x657495
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Zhu, Chu-Hong
中科院分区：
文献类型：
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作者：
Shen, Lei;Zeng, Wen;Zhu, Chu-Hong
血管生成是糖尿病足创面愈合的主要障碍。间充质干细胞（MSCs）在创伤修复中具有重要功能，神经营养因子-3 （NT-3）可促进神经再生和血管生成。我们研究了NT-3通过改善人骨髓间充质干细胞（hMSC）的激活来加速糖尿病足伤口愈合的作用。在体外，NT-3显著促进hMSCs中VEGF、NGF和BDNF的分泌。NT-3改善hMSC条件培养基的活化，促进人脐静脉内皮细胞（HUVEC）的增殖和迁移，显著提高HUVEC划痕的闭合率。此外，我们还利用聚乳酸、混丝和胶原蛋白，通过静电纺丝技术制备了纳米纤维网状生物组织材料。将NT-3刺激的hMSCs植入材料中。与对照组相比，生物组织材料中nt -3刺激的hMSCs显著促进糖尿病C57BL/6J小鼠足部血管生成，加速糖尿病足部创面愈合。这些结果表明NT-3显著促进hMSC中VEGF、NGF和其他血管活性因子的分泌，并通过改善血管内皮细胞的活化诱导血管生成，从而加速伤口愈合。NT-3刺激的hMSCs可以产生加速糖尿病足和其他缺血性溃疡伤口愈合的物质。
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.