EPhrinB2-modified mesenchymal stem cells help repair brain injury in a rat model of cerebral palsy
10.3760/cma.j.issn.0254-1424.2018.11.003
- VernacularTitle:慢病毒介导EP hrinB2基因转染骨髓间充质干细胞对脑瘫大鼠脑损伤的保护作用
- Author:
Min ZHU
1
;
Yue ZHANG
;
Jian TANG
;
Senjie DU
;
Yu HUA
;
Dalin FU
;
Fen LU
;
Hongying LI
;
Xiaoke ZHAO
Author Information
1. 南京医科大学附属儿童医院康复科
- Keywords:
EPhrinB2;
Bone marrow;
Mesenchymal stem cells;
Neurons;
Cerebral palsy
- From:
Chinese Journal of Physical Medicine and Rehabilitation
2018;40(11):814-820
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate any protective effect of transplanting EPhrinB2-modified bone marrow mesenchymal stem cells ( BMSCs) with a rat model of cerebral palsy. Methods BMSCs were isolated and cultured, then further modified by lentivirus-mediated transfection of the EPhrinB2 gene. Ninety-six Sprague-Dawley rats were randomly divided into a sham group, a solvent control group ( PBS group) , an empty lentivirus group ( EGFP group) and an EPhrinB2 recombinant lentivirus group ( EPhrinB2 group) , each of 24. A model of cerebral palsy was estab-lished in the rats of the PBS, EGFP and EPhrinB2 groups using hypoxic-ischemic encephalopathy. Seven days after the operation, the lateral ventricles of the PBS, EGFP and EPhrinB2 group mice were injected with phosphate-buff-ered saline solution, BMSCs or EPhrinB2-modified BMSCs respectively. EPhrinB2 protein expression in the hippo-campus was detected using immunohistochemistry 28 days after the operation. The neuron density in the CA1 region of the hippocampus was observed using hematoxylin and eosin staining, and any apoptosis of hippocampal neurons was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling. The expression of nestin and CD31 in the hippocampus was observed using immunofluorescence assays. Morris water maze testing was also conducted to e-valuate changes in learning and memory ability. Results Compared with the other 3 groups, a significant increase in the expression of protein EPhrinB2 was observed in the hippocampuses of the EPhrinB2 group rats. The pathologi-cal changes in the hippocampus among the EPhrinB2 group were significantly less severe than those in the PBS and EGFP groups. The rate of apoptosis in the hippocampuses of the EPhrinB2 group was significantly lower than that of the other groups. Immunofluorescence showed that nestin- and CD31-positive cells were significantly more numerous in the EPhrinB2 group than in the others. In the water maze the average latency of the EPhrinB2 group was signifi-cantly shorter than those of the other groups. Conclusion Lentiviral-mediated EPhrinb2 transfection of BMSCs into the hippocampus can promote EPhrinB2 gene expression, promote angiogenesis and neuron differentiation, inhibit ap-optosis and accelerate the repair of injured nerves.
