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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BMC
2023-09-01
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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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