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骨间充质干细胞和软骨素酶 ABC 联合应用对大鼠去细胞神经同种异体移植后神经再生的协同作用。

Synergistic effects of bone mesenchymal stem cells and chondroitinase ABC on nerve regeneration after acellular nerve allograft in rats.

机构信息

Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China.

出版信息

Cell Mol Neurobiol. 2012 Apr;32(3):361-71. doi: 10.1007/s10571-011-9764-4. Epub 2011 Nov 18.

Abstract

This study aimed to evaluate whether combination therapy of bone marrow stromal cells (BMSCs) transplantation and chondroitinase ABC (ChABC) treatment further enhances axonal regeneration and functional recovery after acellular nerve allograft repair of the sciatic nerve gap in rats. Eight Sprague-Dawley rats were used as nerve donors, and 32 Wistar rats were randomly divided into four groups: Group I: acellular rat sciatic nerve (ARSN) group; Group II: ChABC treatment; Group III: BMSCs transplantation; and Group IV: ChABC treatment and BMSCs transplantation. The results showed that compared with ARSN control group, BMSC transplantation promoted axonal regeneration, the secretion of neural trophic factors NGF, BDNF and axon angiogenesis in nerve graft. ChABC treatment degraded chondroitin sulfate proteoglycans in ARSN in vitro and in vivo and improved BMSCs survival in ARSN. The combination therapy caused much better beneficial effects evidenced by increasing sciatic function index, nerve conduction velocity, restoration rate of tibialis anterior wet muscle weight, and myelinated nerve number, but did not further boost the therapeutic effects on neurotrophic factor production, axon angiogenesis, and sensory functional recovery by BMSC transplantation. Taken together, for the first time, we demonstrate the synergistic effects of BMSC transplantation and BMSCs treatment on peripheral nerve regeneration, and our findings may help establish novel strategies for cell transplantation therapy for peripheral nerve injury.

摘要

本研究旨在评估骨髓基质细胞(BMSCs)移植联合软骨素酶 ABC(ChABC)治疗是否能进一步增强去细胞神经同种异体修复大鼠坐骨神经间隙后的轴突再生和功能恢复。8 只 Sprague-Dawley 大鼠作为神经供体,32 只 Wistar 大鼠随机分为 4 组:I 组:去细胞大鼠坐骨神经(ARSN)组;II 组:ChABC 治疗组;III 组:BMSCs 移植组;IV 组:ChABC 治疗和 BMSCs 移植组。结果表明,与 ARSN 对照组相比,BMSC 移植促进了轴突再生、神经营养因子 NGF、BDNF 的分泌和神经移植物中的轴突血管生成。ChABC 治疗在体外和体内降解了 ARSN 中的软骨素硫酸盐蛋白聚糖,并提高了 ARSN 中 BMSCs 的存活率。联合治疗通过增加坐骨神经功能指数、神经传导速度、比目鱼肌湿重恢复率和有髓神经数量,产生了更好的有益效果,但并没有进一步增强 BMSC 移植对神经营养因子产生、轴突血管生成和感觉功能恢复的治疗效果。总之,我们首次证明了 BMSC 移植和 ChABC 治疗对周围神经再生的协同作用,我们的研究结果可能有助于为周围神经损伤的细胞移植治疗建立新的策略。

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