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

Background: 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 ex...

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Autores principales:	Zhao-Hui Liang, Jian-Juan Gu, Wen-Xiu Yu, Yun-Qian Guan, Mostafa Khater, Xiao-Bo Li
Formato:	article
Lenguaje:	EN
Publicado:	KeAi Communications Co., Ltd. 2020
Materias:	Cerebral infarction Mesenchymal stem cell Transplantation Transforming growth factor-β1 Microglia Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d1f9cdd7546e487ea4524796439a2080
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spelling	oai:doaj.org-article:d1f9cdd7546e487ea4524796439a20802021-12-02T18:12:37ZBone marrow mesenchymal stem cell transplantation downregulates plasma level and the microglia expression of transforming growth factor β1 in the acute phase of cerebral cortex ischemia2095-882X10.1016/j.cdtm.2020.05.005https://doaj.org/article/d1f9cdd7546e487ea4524796439a20802020-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2095882X2030044Xhttps://doaj.org/toc/2095-882XBackground: 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. Methods: 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. Results: 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 < 0.01); the number of TGF-β1+ cells after transplantation (35.00 ± 13.66 cells/mm2) was significantly reduced in comparison to that in the ischemic control group (72.33 ± 32.08 cells/mm2) (F = 37.680, P < 0.01). The number of TGF-β1+/Iba-1+ microglia cells in the transplantation group (3.67 ± 3.17 cells/mm2) was significantly reduced in comparison to that of the ischemic control group (13.67 ± 5.52 cells/mm2) (F = 29.641, P < 0.01). The proportion of TGF-β1+/Iba-1+ microglia cells out of all Iba-1+ microglia cells after transplantation (4.38 ± 3.18%) was significantly decreased compared with that in the ischemic control group (12.81 ± 4.86%) (F = 28.125, P < 0.01). Conclusions: Iba-1+ microglia is one of the main cell types that express TGF-β1. Intravenous transplantation of BM-MSCs does not cooperate with TGF-β1+ cells in immune-regulation, but reduces the TGF-β1 content in the infarcted area and in the plasma at 48 h after cerebral infarction.Zhao-Hui LiangJian-Juan GuWen-Xiu YuYun-Qian GuanMostafa KhaterXiao-Bo LiKeAi Communications Co., Ltd.articleCerebral infarctionMesenchymal stem cellTransplantationTransforming growth factor-β1MicrogliaMedicine (General)R5-920ENChronic Diseases and Translational Medicine, Vol 6, Iss 4, Pp 270-280 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cerebral infarction Mesenchymal stem cell Transplantation Transforming growth factor-β1 Microglia Medicine (General) R5-920
spellingShingle	Cerebral infarction Mesenchymal stem cell Transplantation Transforming growth factor-β1 Microglia Medicine (General) R5-920 Zhao-Hui Liang Jian-Juan Gu Wen-Xiu Yu Yun-Qian Guan Mostafa Khater Xiao-Bo Li 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
description	Background: 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. Methods: 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. Results: 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 < 0.01); the number of TGF-β1+ cells after transplantation (35.00 ± 13.66 cells/mm2) was significantly reduced in comparison to that in the ischemic control group (72.33 ± 32.08 cells/mm2) (F = 37.680, P < 0.01). The number of TGF-β1+/Iba-1+ microglia cells in the transplantation group (3.67 ± 3.17 cells/mm2) was significantly reduced in comparison to that of the ischemic control group (13.67 ± 5.52 cells/mm2) (F = 29.641, P < 0.01). The proportion of TGF-β1+/Iba-1+ microglia cells out of all Iba-1+ microglia cells after transplantation (4.38 ± 3.18%) was significantly decreased compared with that in the ischemic control group (12.81 ± 4.86%) (F = 28.125, P < 0.01). Conclusions: Iba-1+ microglia is one of the main cell types that express TGF-β1. Intravenous transplantation of BM-MSCs does not cooperate with TGF-β1+ cells in immune-regulation, but reduces the TGF-β1 content in the infarcted area and in the plasma at 48 h after cerebral infarction.
format	article
author	Zhao-Hui Liang Jian-Juan Gu Wen-Xiu Yu Yun-Qian Guan Mostafa Khater Xiao-Bo Li
author_facet	Zhao-Hui Liang Jian-Juan Gu Wen-Xiu Yu Yun-Qian Guan Mostafa Khater Xiao-Bo Li
author_sort	Zhao-Hui Liang
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	KeAi Communications Co., Ltd.
publishDate	2020
url	https://doaj.org/article/d1f9cdd7546e487ea4524796439a2080
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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

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