Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemia

Abstract Background To explore whether local transplantation of mesenchymal stem cells (MSCs) in temporal muscle can promote collateral angiogenesis and to analyze its main mechanisms of promoting angiogenesis. Methods Bilateral carotid artery stenosis (BCAS) treated mice were administrated with enc...

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Main Authors: Xincheng Zhang, Yimin Huang, Yuan Liu, Yanchao Liu, Xuejun He, Xiaopeng Ma, Chao Gan, Xin Zou, Sheng Wang, Kai Shu, Ting Lei, Huaqiu Zhang
Format: Article
Language:English
Published: BMC 2023-09-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-023-03465-7
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author Xincheng Zhang
Yimin Huang
Yuan Liu
Yanchao Liu
Xuejun He
Xiaopeng Ma
Chao Gan
Xin Zou
Sheng Wang
Kai Shu
Ting Lei
Huaqiu Zhang
author_facet Xincheng Zhang
Yimin Huang
Yuan Liu
Yanchao Liu
Xuejun He
Xiaopeng Ma
Chao Gan
Xin Zou
Sheng Wang
Kai Shu
Ting Lei
Huaqiu Zhang
author_sort Xincheng Zhang
collection DOAJ
description Abstract Background To explore whether local transplantation of mesenchymal stem cells (MSCs) in temporal muscle can promote collateral angiogenesis and to analyze its main mechanisms of promoting angiogenesis. Methods Bilateral carotid artery stenosis (BCAS) treated mice were administrated with encephalo-myo-synangiosis (EMS), and bone marrow mesenchymal stem cells (BMSCs) were transplanted into the temporal muscle near the cerebral cortex. On the 30th day after EMS, the Morris water maze, immunofluorescence, laser speckle imaging, and light sheet microscopy were performed to evaluate angiogenesis; In addition, rats with bilateral common carotid artery occlusion were also followed by EMS surgery, and BMSCs from GFP reporter rats were transplanted into the temporal muscle to observe the survival time of BMSCs. Then, the concentrated BMSC-derived conditioned medium (BMSC-CM) was used to stimulate HUVECs and BMECs for ki-67 immunocytochemistry, CCK-8, transwell and chick chorioallantoic membrane assays. Finally, the cortical tissue near the temporal muscle was extracted after EMS, and proteome profiler (angiogenesis array) as well as RT-qPCR of mRNA or miRNA was performed. Results The results of the Morris water maze 30 days after BMSC transplantation in BCAS mice during the EMS operation, showed that the cognitive impairment in the BCAS + EMS + BMSC group was alleviated (P < 0.05). The results of immunofluorescence, laser speckle imaging, and light sheet microscopy showed that the number of blood vessels, blood flow and astrocytes increased in the BCAS + EMS + BMSC group (P < 0.05). The BMSCs of GFP reporter rats were applied to EMS and showed that the transplanted BMSCs could survive for up to 14 days. Then, the results of ki-67 immunocytochemistry, CCK-8 and transwell assays showed that the concentrated BMSC-CM could promote the proliferation and migration of HUVECs and BMECs (P < 0.05). Finally, the results of proteome profiler (angiogenesis array) in the cerebral cortex showed that the several pro-angiogenesis factors (such as MMP-3, MMP-9, IGFBP-2 or IGFBP-3) were notably highly expressed in MSC transplantation group compared to others. Conclusions Local MSCs transplantation together with EMS surgery can promote angiogenesis and cognitive behavior in chronic brain ischemia mice. Our study illustrated that MSC local transplantation can be the potential therapeutical option for improving EMS treatment efficiency which might be translated into clinical application.
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spelling doaj.art-9eb5a16e8878425d90183eaae795ce972023-11-19T12:33:17ZengBMCStem Cell Research & Therapy1757-65122023-09-0114111710.1186/s13287-023-03465-7Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemiaXincheng Zhang0Yimin Huang1Yuan Liu2Yanchao Liu3Xuejun He4Xiaopeng Ma5Chao Gan6Xin Zou7Sheng Wang8Kai Shu9Ting Lei10Huaqiu Zhang11Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyAbstract Background To explore whether local transplantation of mesenchymal stem cells (MSCs) in temporal muscle can promote collateral angiogenesis and to analyze its main mechanisms of promoting angiogenesis. Methods Bilateral carotid artery stenosis (BCAS) treated mice were administrated with encephalo-myo-synangiosis (EMS), and bone marrow mesenchymal stem cells (BMSCs) were transplanted into the temporal muscle near the cerebral cortex. On the 30th day after EMS, the Morris water maze, immunofluorescence, laser speckle imaging, and light sheet microscopy were performed to evaluate angiogenesis; In addition, rats with bilateral common carotid artery occlusion were also followed by EMS surgery, and BMSCs from GFP reporter rats were transplanted into the temporal muscle to observe the survival time of BMSCs. Then, the concentrated BMSC-derived conditioned medium (BMSC-CM) was used to stimulate HUVECs and BMECs for ki-67 immunocytochemistry, CCK-8, transwell and chick chorioallantoic membrane assays. Finally, the cortical tissue near the temporal muscle was extracted after EMS, and proteome profiler (angiogenesis array) as well as RT-qPCR of mRNA or miRNA was performed. Results The results of the Morris water maze 30 days after BMSC transplantation in BCAS mice during the EMS operation, showed that the cognitive impairment in the BCAS + EMS + BMSC group was alleviated (P < 0.05). The results of immunofluorescence, laser speckle imaging, and light sheet microscopy showed that the number of blood vessels, blood flow and astrocytes increased in the BCAS + EMS + BMSC group (P < 0.05). The BMSCs of GFP reporter rats were applied to EMS and showed that the transplanted BMSCs could survive for up to 14 days. Then, the results of ki-67 immunocytochemistry, CCK-8 and transwell assays showed that the concentrated BMSC-CM could promote the proliferation and migration of HUVECs and BMECs (P < 0.05). Finally, the results of proteome profiler (angiogenesis array) in the cerebral cortex showed that the several pro-angiogenesis factors (such as MMP-3, MMP-9, IGFBP-2 or IGFBP-3) were notably highly expressed in MSC transplantation group compared to others. Conclusions Local MSCs transplantation together with EMS surgery can promote angiogenesis and cognitive behavior in chronic brain ischemia mice. Our study illustrated that MSC local transplantation can be the potential therapeutical option for improving EMS treatment efficiency which might be translated into clinical application.https://doi.org/10.1186/s13287-023-03465-7Mesenchymal stem cellsEncephalo-myo-synangiosisAngiogenesisMoyamoya diseaseCell transplantation
spellingShingle Xincheng Zhang
Yimin Huang
Yuan Liu
Yanchao Liu
Xuejun He
Xiaopeng Ma
Chao Gan
Xin Zou
Sheng Wang
Kai Shu
Ting Lei
Huaqiu Zhang
Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemia
Stem Cell Research & Therapy
Mesenchymal stem cells
Encephalo-myo-synangiosis
Angiogenesis
Moyamoya disease
Cell transplantation
title Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemia
title_full Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemia
title_fullStr Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemia
title_full_unstemmed Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemia
title_short Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemia
title_sort local transplantation of mesenchymal stem cells improves encephalo myo synangiosis mediated collateral neovascularization in chronic brain ischemia
topic Mesenchymal stem cells
Encephalo-myo-synangiosis
Angiogenesis
Moyamoya disease
Cell transplantation
url https://doi.org/10.1186/s13287-023-03465-7
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