Hypoxic preconditioned bone mesenchymal stem cells ameliorate spinal cord injury in rats via improved survival and migration

被引:38
作者
Wang, Weiheng [1 ]
Huang, Xiaodong [1 ]
Lin, Wenbo [1 ]
Qiu, Yuanyuan [2 ]
He, Yunfei [1 ,3 ]
Yu, Jiangming [1 ]
Xi, Yanhai [1 ]
Ye, Xiaojian [1 ]
机构
[1] Second Mil Med Univ, Changzheng Hosp, Dept Orthoped, 415 Fengyang Rd, Shanghai 200003, Peoples R China
[2] Shanghai Elect Power Hosp, Dept Resp, Shanghai 200050, Peoples R China
[3] Lanzhou Gen Hosp Lanzhou Mil Command Reg, Dept Orthoped, Lanzhou 730050, Gansu, Peoples R China
基金
中国国家自然科学基金;
关键词
spinal cord injury; cell therapy; bone marrow mesenchymal stem cells; hypoxic; migration; differentiation; MARROW STROMAL CELLS; URINARY-TRACT DYSFUNCTION; LUMBAR PUNCTURE; CEREBRAL-CORTEX; IN-VITRO; TRANSPLANTATION; REPAIR; CONTUSION; EXPRESSION; DELIVERY;
D O I
10.3892/ijmm.2018.3810
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The unique hypoxic inflammatory microenvironment observed in the spinal cord following spinal cord injury (SCI) limits the survival and efficacy of transplanted bone mesenchymal stem cells (BMSCs). The aim of the present study was to determine whether hypoxic preconditioning (HP) increased the therapeutic effects of BMSC on SCI. BMSCs were pretreated with cobalt chloride (CoCl2) in vitro, and the proliferative apoptotic and migratory abilities of these hypoxic BMSCs (H-BMSCs) were assessed. BMSCs and H-BMSCs derived from green fluorescent protein (GFP) rats were transplanted into SCI rats in vivo. The neurological function, histopathology, inflammation, and number and migration of transplanted cells were examined. HP significantly enhanced BMSC migration (increased hypoxia inducible factor 1 and C-X-C motif chemokine receptor 4 expression) and tolerance to apoptotic conditions (decreased caspase-3 and increased B-cell lymphoma 2 expression) in vitro. In vivo, H-BMSC transplantation significantly improved neurological function, decreased spinal cord damage and suppressed the inflammatory response associated with microglial activation. The number of GFP-positive cells in the SCI core and peripheral region of H-BMSC animals was increased compared with that in those of BMSC animals, suggesting that HP may increase the survival and migratory abilities of BMSCs and highlights their therapeutic potential for SCI.
引用
收藏
页码:2538 / 2550
页数:13
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