Delayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in mice
Abstract Background Stroke is a leading cause of death and disability worldwide, yet there are limited treatments available. Intranasal administration is a novel non-invasive strategy to deliver cell therapy into the brain. Cells delivered via the intranasal route can migrate from the nasal mucosa t...
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | BMC Neuroscience |
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| Online Access: | http://link.springer.com/article/10.1186/s12868-018-0418-z |
| _version_ | 1811203801243189248 |
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| author | Monica J. Chau Todd C. Deveau Xiaohuan Gu Yo Sup Kim Yun Xu Shan Ping Yu Ling Wei |
| author_facet | Monica J. Chau Todd C. Deveau Xiaohuan Gu Yo Sup Kim Yun Xu Shan Ping Yu Ling Wei |
| author_sort | Monica J. Chau |
| collection | DOAJ |
| description | Abstract Background Stroke is a leading cause of death and disability worldwide, yet there are limited treatments available. Intranasal administration is a novel non-invasive strategy to deliver cell therapy into the brain. Cells delivered via the intranasal route can migrate from the nasal mucosa to the ischemic infarct and show acute neuroprotection as well as functional benefits. However, there is little information about the regenerative effects of this transplantation method in the delayed phase of stroke. We hypothesized that repeated intranasal deliveries of bone marrow stromal cells (BMSCs) would be feasible and could enhance delayed neurovascular repair and functional recovery after ischemic stroke. Results Reverse transcription polymerase chain reaction and immunocytochemistry were performed to analyze the expression of regenerative factors including SDF-1α, CXCR4, VEGF and FAK in BMSCs. Ischemic stroke targeting the somatosensory cortex was induced in adult C57BL/6 mice by permanently occluding the right middle cerebral artery and temporarily occluding both common carotid arteries. Hypoxic preconditioned (HP) BMSCs (HP-BMSCs) with increased expression of surviving factors HIF-1α and Bcl-xl (1 × 106 cells/100 μl per mouse) or cell media were administered intranasally at 3, 4, 5, and 6 days after stroke. Mice received daily BrdU (50 mg/kg) injections until sacrifice. BMSCs were prelabeled with Hoechst 33342 and detected within the peri-infarct area 6 and 24 h after transplantation. In immunohistochemical staining, significant increases in NeuN/BrdU and Glut-1/BrdU double positive cells were seen in stroke mice received HP-BMSCs compared to those received regular BMSCs. HP-BMSC transplantation significantly increased local cerebral blood flow and improved performance in the adhesive removal test. Conclusions This study suggests that delayed and repeated intranasal deliveries of HP-treated BMSCs is an effective treatment to encourage regeneration after stroke. |
| first_indexed | 2024-04-12T03:01:18Z |
| format | Article |
| id | doaj.art-f7dfb68b6a9741adb66d53a87128ddaa |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-04-12T03:01:18Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-f7dfb68b6a9741adb66d53a87128ddaa2022-12-22T03:50:40ZengBMCBMC Neuroscience1471-22022018-04-0119111210.1186/s12868-018-0418-zDelayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in miceMonica J. Chau0Todd C. Deveau1Xiaohuan Gu2Yo Sup Kim3Yun Xu4Shan Ping Yu5Ling Wei6Department of Anesthesiology, Emory University School of MedicineDepartment of Anesthesiology, Emory University School of MedicineDepartment of Anesthesiology, Emory University School of MedicineDepartment of Anesthesiology, Emory University School of MedicineDepartment of Neurology, Nanjing University School of MedicineDepartment of Anesthesiology, Emory University School of MedicineDepartment of Anesthesiology, Emory University School of MedicineAbstract Background Stroke is a leading cause of death and disability worldwide, yet there are limited treatments available. Intranasal administration is a novel non-invasive strategy to deliver cell therapy into the brain. Cells delivered via the intranasal route can migrate from the nasal mucosa to the ischemic infarct and show acute neuroprotection as well as functional benefits. However, there is little information about the regenerative effects of this transplantation method in the delayed phase of stroke. We hypothesized that repeated intranasal deliveries of bone marrow stromal cells (BMSCs) would be feasible and could enhance delayed neurovascular repair and functional recovery after ischemic stroke. Results Reverse transcription polymerase chain reaction and immunocytochemistry were performed to analyze the expression of regenerative factors including SDF-1α, CXCR4, VEGF and FAK in BMSCs. Ischemic stroke targeting the somatosensory cortex was induced in adult C57BL/6 mice by permanently occluding the right middle cerebral artery and temporarily occluding both common carotid arteries. Hypoxic preconditioned (HP) BMSCs (HP-BMSCs) with increased expression of surviving factors HIF-1α and Bcl-xl (1 × 106 cells/100 μl per mouse) or cell media were administered intranasally at 3, 4, 5, and 6 days after stroke. Mice received daily BrdU (50 mg/kg) injections until sacrifice. BMSCs were prelabeled with Hoechst 33342 and detected within the peri-infarct area 6 and 24 h after transplantation. In immunohistochemical staining, significant increases in NeuN/BrdU and Glut-1/BrdU double positive cells were seen in stroke mice received HP-BMSCs compared to those received regular BMSCs. HP-BMSC transplantation significantly increased local cerebral blood flow and improved performance in the adhesive removal test. Conclusions This study suggests that delayed and repeated intranasal deliveries of HP-treated BMSCs is an effective treatment to encourage regeneration after stroke.http://link.springer.com/article/10.1186/s12868-018-0418-zIschemic strokeBMSCIntranasalHypoxic preconditioningTrophic factors |
| spellingShingle | Monica J. Chau Todd C. Deveau Xiaohuan Gu Yo Sup Kim Yun Xu Shan Ping Yu Ling Wei Delayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in mice BMC Neuroscience Ischemic stroke BMSC Intranasal Hypoxic preconditioning Trophic factors |
| title | Delayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in mice |
| title_full | Delayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in mice |
| title_fullStr | Delayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in mice |
| title_full_unstemmed | Delayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in mice |
| title_short | Delayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in mice |
| title_sort | delayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in mice |
| topic | Ischemic stroke BMSC Intranasal Hypoxic preconditioning Trophic factors |
| url | http://link.springer.com/article/10.1186/s12868-018-0418-z |
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