Calpain inhibitor attenuates ER stress-induced apoptosis in injured spinal cord after bone mesenchymal stem cells transplantation
Calpain inhibitor attenuates ER stress-induced apoptosis in injured spinal cord after bone mesenchymal stem cells transplantation
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钙蛋白酶抑制剂可减弱骨髓间充质干细胞移植后损伤脊髓中内质网应激诱导的细胞凋亡
DOI：
10.1016/j.neuint.2016.04.015
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发表时间：
2016-07-01
影响因子：
4.2
通讯作者：
Zhang, Xiaoming
中科院分区：
文献类型：
--
作者：
Wang, Chao;Shi, Dongling;Zhang, Xiaoming
骨髓间充质干细胞（BMSCs）用于组织修复的治疗受到脊髓损伤（SCI）后移植到受体部位的细胞存活率低的限制。在此，我们研究了钙蛋白酶抑制剂（MDL 28170）对骨髓间充质干细胞存活的大鼠脊髓损伤模型在体外和体内的影响。收集缺氧损伤的VSC4.1运动神经元的条件培养基（Hypoxia-CM）以模拟损伤脊髓的微环境。衣霉素也用于诱导BMSCs的内质网（ER）应激。CCK-8法、LDH漏出法和流式细胞仪检测结果表明MDL 28170能增强低氧-CM和衣霉素诱导的BMSCs存活。此外，MDL 28170显着提高GFP阳性骨髓基质细胞移植到脊髓损伤大鼠的挫伤后，在体内的生存。MDL 28170对BMSCs存活的保护作用可能与抑制calpain的激活及下游内质网应激诱导的细胞凋亡有关。本研究结果首次提示MDL 28170与骨髓间充质干细胞联合移植可通过调节内质网应激诱导的细胞凋亡来挽救损伤脊髓中的细胞。钙蛋白酶抑制剂MDL 28170可能为促进移植BMSCs在细胞再生医学中的存活提供新的策略。(C)2016爱思唯尔有限公司版权所有
Bone marrow mesenchymal stem cells (BMSCs) therapy for tissue repair is limited by low survival of cells transplanted in the recipient sites after spinal cord injury (SCI). Here, we investigated the effects of a calpain inhibitor (MDL28170) on BMSCs survival by a rat model of spinal cord injury in vitro and in vivo. Conditioned medium from hypoxia injured VSC4.1 motor neurons (Hypoxia-CM) were collected to mimic the micro-environment of injured spinal cord. Tunicamycin was also applied to induce endoplasmic reticulum (ER) stress in BMSCs. The CCK-8 assay, LDH leakage assay and flow cytometer assay demonstrated that MDL28170 could enhance BMSCs survival in response to Hypoxia-CM and tunicamycin. Moreover, MDL28170 significantly enhanced GFP-positive BMSCs survival in vivo after transplantation into the contused spinal cord of SCI rats. The protective effects of MDL28170 on BMSCs survival may inhibit the activation of calpain and the downstream ER stress-induced apoptosis. The present results suggested for the first time that MDL28170 with BMSCs transplant helped to rescue cells in injured spinal cord by modulating the ER stress-induced apoptosis. The calpain inhibitor, MDL28170 may have the promising new strategies for promoting the survival of transplanted BMSCs on cell-based regenerative medicine. (C) 2016 Elsevier Ltd. All rights reserved.