Intravenous transplantation of allogeneic bone marrow derived mesenchymal stromal cells at early stage of cortex ischemia significantly increases number of Iba-1+ microglia cells expressed brain-derived neurotrophic factor in the infarct area of rats
10.3760/cma.j.issn.1671-8925.2019.05.001
- VernacularTitle:脑梗死大鼠早期静脉移植BM-MSCs可诱导皮层梗死区表达BDNF的Iba-1+小胶质细胞显著增加
- Author:
Xiaobo LI
1
;
Haiqiang ZOU
;
Chunsong ZHAO
;
Renchao ZHAO
;
Min HUANG
;
Yao LIU
;
Yunqian GUAN
Author Information
1. 苏北人民医院神经内科
- Keywords:
Cerebral infarct;
Mesenchymal stromal cell;
Microglia;
Brain-derived neurotrophic factor;
Cell transplantation
- From:
Chinese Journal of Neuromedicine
2019;18(5):433-441
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the main cell types expressed brain-derived neurotrophic factor (BDNF) in the posterior cortical infarction area in cerebral infarction rats after early vein allograft of bone marrow mesenchymal stem cells (BM-MSCs) and the effect of BM-MSCs transplantation on their ce11 numbers and percentages.Methods (1) Fifteen SD rats were randomly divided into sham-operated group 1,ischemia control group 1,and BM-MSCs transplantation group 1 (n=5);distal middle cerebral artery occlusion (dMCA) models were used in the later two groups;1 × 106 CM-DiI labeled BM-MSCs were intravascularly transplanted into the tail vein of rats from the transplantation group 1 at one h after ischemia;all rats were sacrificed 48 h after ischemia;BM-MSCs with co-existence of CM-Dil and BDNF in the ischemia cortex areas were detected by immunofluorescence staining.(2)Fifteen SD rats were randomly divided into sham-operated group 2,ischemia control group 2,and BM-MSCs transplantation group 2 (n=5);dMCAO models were used in the later two groups;1 ×106 non-labeled BM-MSCs were intravascularly transplanted into the tail vein of rats from the transplantation group 2 at one h after ischemia;48 h after ischemia onset,all rats were sacrificed;the number of BDNF+ and CD68+ microglia cells,BDNF+ and Iba-1+ microglia cells,and BDNF+ and neuron-specific nucleoprotein (NeuN)+ neurons were measured by immunofluorescence staining.Results (1) CM-Dil red fluorescence labeled allogeneic BM-MSCs were only found in BM-MSCs transplantation group 1;the labeled cells scattered in the infarct and peri-infarct cortices;9.70％±3.47％ CM-Dil labeled BM-MSCs expressed BDNF,accounting for 13.32％±4.48％ of all BDNF+ cells in the infarct brain cortex.(2) In the brain tissues of cortex infarct area of BM-MSCs transplantation group 2,38.40％±9.04％ BDNF+ cells were Iba-1+ microglia cells,11.65％±2.76％ BDNF+ cells were CD68+ microglia cells,and 28.96％±6.99％ BDNF+ cells were NeuN+ neurons;the Iba-1+ cell numbers and Iba-1+/BDNF+ double positive cell percentages in the BM-MSCs transplantation group 2 ([92.06±36.52]/mm2 and 79.21％±12.27％) were significantly increased as compared with those in the ischemia control group 2 ([31.13±10.23] mm2 and 60.15％±28.20％,P＜0.05).Conclusion Allogeneic BM-MSCs is capable of migrating into the infarct cortex when intravenous transplantation of BM-MSCs is performed at the early stage after ischemia;the main sources of BDNF in these areas are microglias cells and neurons;these BM-MSCs increase both number and percentage of Iba-1+/BDNF+ double positive cells,which may be one of the underlying mechanisms of therapeutic effects.
