Thrombospondin-1 modified bone marrow mesenchymal stem cells (BMSCs) promote neurite outgrowth and functional recovery in rats with spinal cord injury.
Thrombospondin-1 modified bone marrow mesenchymal stem cells (BMSCs) promote neurite outgrowth and functional recovery in rats with spinal cord injury.
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Thrombospondin-1 修饰的骨髓间充质干细胞 (BMSC) 促进脊髓损伤大鼠神经突生长和功能恢复
DOI：
10.18632/oncotarget.22018
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发表时间：
2017-11-10
期刊：
影响因子：
--
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Pu Y;Meng K;Gu C;Wang L;Zhang X
干细胞疗法目前在脊髓损伤（SCI）的治疗中获得了动力。然而，不能满足的内在神经突起生长能力构成了损伤脊髓修复的重大障碍，并最终导致神经功能障碍。本研究评价了促轴突生长分子血小板反应蛋白-1（TSP-1）、修饰的骨髓间充质干细胞（BMSCs）在体外和体内促进氧葡萄糖脱氢酶（OGD）处理的运动神经元和SCI大鼠模型的轴突生长的功效。目前的结果表明，BMSC +TSP-1治疗可以促进SCI后神经突起长度、神经元存活和功能恢复。此外，TSP-1还可激活转化生长因子-β1（TGF-β1），诱导Smad 2磷酸化，促进GAP-43表达，促进神经突起生长。本研究首次证实BMSCs+TSP-1可部分通过TGF-β1/p-Samd 2途径促进脊髓损伤后神经突起生长和功能恢复。本研究为TSP-1修饰BMSCs治疗脊髓损伤提供了新的证据。
Stem cell therapies are currently gaining momentum in the treatment of spinal cord injury (SCI). However, unsatisfied intrinsic neurite growth capacity constitutes significant obstacles for injured spinal cord repair and ultimately results in neurological dysfunction. The present study assessed the efficacy of thrombospondin-1 (TSP-1), a neurite outgrowth-promoting molecule, modified bone marrow mesenchymal stem cells (BMSCs) on promoting neurite outgrowth in vitro and in vivo of Oxygen–Glucose Deprivation (OGD) treated motor neurons and SCI rat models. The present results demonstrated that the treatment of BMSCs+TSP-1 could promote the neurite length, neuronal survival, and functional recovery after SCI. Additionally, TSP-1 could activate transforming growth factor-β1 (TGF-β1) then induced the smad2 phosphorylation, and expedited the expression of GAP-43 to promote neurite outgrowth. The present study for the first time demonstrated that BMSCs+TSP-1 could promote neurite outgrowth and functional recovery after SCI partly through the TGF-β1/p-Samd2 pathway. The study provided a novel encouraging evidence for the potential treatment of BMSCs modification with TSP-1 in patients with SCI.
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