Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke
Abstract Background Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intrace...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-023-03236-4 |
| _version_ | 1797827675835858944 |
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| author | Satoru Yabuno Takao Yasuhara Takayuki Nagase Satoshi Kawauchi Chiaki Sugahara Yosuke Okazaki Kakeru Hosomoto Susumu Sasada Tatsuya Sasaki Naoki Tajiri Cesar V. Borlongan Isao Date |
| author_facet | Satoru Yabuno Takao Yasuhara Takayuki Nagase Satoshi Kawauchi Chiaki Sugahara Yosuke Okazaki Kakeru Hosomoto Susumu Sasada Tatsuya Sasaki Naoki Tajiri Cesar V. Borlongan Isao Date |
| author_sort | Satoru Yabuno |
| collection | DOAJ |
| description | Abstract Background Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke. Methods Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 105 cells/5 μl) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups. Results SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05). Conclusions This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF. |
| first_indexed | 2024-04-09T12:52:09Z |
| format | Article |
| id | doaj.art-e46a2bf2f12742408b977596f515937d |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-09T12:52:09Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-e46a2bf2f12742408b977596f515937d2023-05-14T11:10:26ZengBMCStem Cell Research & Therapy1757-65122023-01-0114111910.1186/s13287-023-03236-4Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic strokeSatoru Yabuno0Takao Yasuhara1Takayuki Nagase2Satoshi Kawauchi3Chiaki Sugahara4Yosuke Okazaki5Kakeru Hosomoto6Susumu Sasada7Tatsuya Sasaki8Naoki Tajiri9Cesar V. Borlongan10Isao Date11Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Sciences and Medical SchoolDepartment of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South FloridaDepartment of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAbstract Background Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke. Methods Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 105 cells/5 μl) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups. Results SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05). Conclusions This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF.https://doi.org/10.1186/s13287-023-03236-4Cerebral ischemic infarctRehabilitationRegenerative medicineSB623Voluntary exercise |
| spellingShingle | Satoru Yabuno Takao Yasuhara Takayuki Nagase Satoshi Kawauchi Chiaki Sugahara Yosuke Okazaki Kakeru Hosomoto Susumu Sasada Tatsuya Sasaki Naoki Tajiri Cesar V. Borlongan Isao Date Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke Stem Cell Research & Therapy Cerebral ischemic infarct Rehabilitation Regenerative medicine SB623 Voluntary exercise |
| title | Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke |
| title_full | Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke |
| title_fullStr | Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke |
| title_full_unstemmed | Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke |
| title_short | Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke |
| title_sort | synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow derived stromal cells sb623 and voluntary exercise with running wheel in a rat model of ischemic stroke |
| topic | Cerebral ischemic infarct Rehabilitation Regenerative medicine SB623 Voluntary exercise |
| url | https://doi.org/10.1186/s13287-023-03236-4 |
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