Bone marrow mesenchymal stem cell transplantation downregulates plasma level and the microglia expression of transforming growth factor β1 in the acute phase of cerebral cortex ischemia

• Published in: Chronic diseases and translational medicine 2020-12, Vol.6 (4), p.270-280
• Main Authors: Liang, Zhao-Hui, Gu, Jian-Juan, Yu, Wen-Xiu, Guan, Yun-Qian, Khater, Mostafa, Li, Xiao-Bo
• Format: Article
• Language: English
• Subjects: Cerebral infarction; Mesenchymal stem cell; Microglia; Original; Transforming growth factor-β1; Transplantation
• ISSN: 2095-882X; 2589-0514; 2589-0514
• DOI: 10.1016/j.cdtm.2020.05.005

Both bone marrow mesenchymal stem cell (BM-MSC) and transforming growth factor-β1 (TGF-β1) have a strong anti-inflammatory capacity in stroke. But their relationship has not been well addressed. In this study, we investigated how intravenous BM-MSC transplantation in rats effected the expression of TGF-β1 48 h post cerebral ischemia, and we analyzed the main cells that produce TGF-β1. We used a distal middle cerebral artery occlusion (dMCAO) model in twenty Sprague–Dawley (SD) rats. The rats were randomly divided into two groups: the ischemic control group and the postischemic BM-MSC transplantation group. One hour after the dMCAO model was established, the rats were injected in the tail vein with either 1 ml saline or 1 × 106 BM-MSCs suspended in 1 ml saline. ELISAs were used to detect TGF-β1 content in the brain infarct core area, striatum and the plasma at 48 h after cerebral infarction. Immunofluorescent staining of brain tissue sections for TGF-β1, Iba-1, CD68 and NeuN was performed to determine the number and the proportion of double stained cells and to detect possible TGF-β1 producing cells in the brain tissue. Forty-eight hours after ischemia, the TGF-β1 content in the infarcted area of the BM-MSC transplantation group (23.94 ± 4.48 pg/ml) was significantly lower than it was in the ischemic control group (34.18 ± 4.32 pg/ml) (F = 13.534, P = 0.006). The TGF-β1 content in the rat plasma in the BM-MSC transplantation group (75.91 ± 12.53 pg/ml) was significantly lower than it was in the ischemic control group (131.18 ± 16.07 pg/ml) (F = 36.779, P = 0.0002), suggesting that after transplantation of BM-MSCs, TGF-β1 levels in the plasma decreased, but there was no significant change in the striatum area. Immunofluorescence staining showed that the total number of nucleated cells (1037.67 ± 222.16 cells/mm2) in the infarcted area after transplantation was significantly higher than that in the ischemic control group (391.67 ± 69.50 cells/mm2) (F = 92.421, P