Therapeutic efficacy of lentiviral vector mediated BDNF gene-modified MSCs in cerebral infarction.
- Author:
Dongyu HUANG
1
;
Zhijian ZHANG
;
Bailing CHEN
;
Xiuli WU
;
Ning WANG
;
Yanding ZHANG
Author Information
1. Department of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Brain-Derived Neurotrophic Factor;
biosynthesis;
genetics;
Genetic Vectors;
genetics;
Infarction, Middle Cerebral Artery;
genetics;
therapy;
Lentivirus;
genetics;
metabolism;
Male;
Mesenchymal Stem Cell Transplantation;
methods;
Mesenchymal Stromal Cells;
cytology;
metabolism;
Rats;
Rats, Inbred F344;
Recovery of Function;
Transfection
- From:
Chinese Journal of Biotechnology
2008;24(7):1174-1179
- CountryChina
- Language:Chinese
-
Abstract:
Pretreatment with brain-derived neurotrophic factor (BDNF) reduces ischemic damage after focal cerebral ischemia, and bone marrow mesenchymal stem cells(MSCs) were reported to ameliorate functional deficits after stroke in rats. Here we investigate the synergistically therapeutic effects of BDNF gene-modified MSCs on cerebral infarction. We transfected MSCs with the BDNF gene using a lentivirus-based system and investigated whether the BDNF-modified MSCs contributed to improved functional recovery in a rat transient middle cerebral artery occlusion (MCAO) model. Compared to untreated rats, rats that received both MSCs and BDNF-MSCs showed significantly more functional recovery. The difference in modified neurological severity score(mNSS) was statistically significant (P < 0.001). Recovery was better in BDNF-MSCs than in MSCs (P < 0.001). At the second week and second month after the systemic delivery of blank vector-modified MSCs and BDNF-modified MSCs, the treated rats exhibited more significant recovery than the control, including the accumulation and living of enhanced green fluorescence protein (EGFP)-positive cells in the infarct area and surrounding areas, neuron-like changes, expression of surface markers of neural cells, and a large amount of BDNF expression in the BDNF-MSCs-treated group. Our findings suggest that BDNF-gene-modified rMSCs can migrate to surrounding areas of the cerebral infarction lesion, differentiate into neural cells, and survive for extended periods. With the synergy of BDNF, they may promote the recovery of the neurological function following cerebral infarction and represent a new strategy for stem cell-based therapy.
