The neuroprotection of hypoxic adipose tissue-derived mesenchymal stem cells in experimental traumatic brain injury
Traumatic brain injury is one of the leading causes of mortality and morbidity worldwide. At present there is no effective treatment. Previous studies have demonstrated that topical application of adipose tissue-derived mesenchymal stem cells can improve functional recovery in experimental traumatic...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2019-07-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/0963689719855624 |
| _version_ | 1818119425695416320 |
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| author | Hui Ma Ping Kuen Lam Cindy See Wai Tong Kin Ki Yan Lo George Kwok Chu Wong Wai Sang Poon |
| author_facet | Hui Ma Ping Kuen Lam Cindy See Wai Tong Kin Ki Yan Lo George Kwok Chu Wong Wai Sang Poon |
| author_sort | Hui Ma |
| collection | DOAJ |
| description | Traumatic brain injury is one of the leading causes of mortality and morbidity worldwide. At present there is no effective treatment. Previous studies have demonstrated that topical application of adipose tissue-derived mesenchymal stem cells can improve functional recovery in experimental traumatic brain injury. In this study, we evaluated whether hypoxic preconditioned mesenchymal stem cells could enhance the recovery from traumatic brain injury. Traumatic brain injury was induced with an electromagnetically controlled cortical impact device. Two million mesenchymal stem cells derived from the adipose tissue of transgenic green fluorescent protein Sprague-Dawley rats were cultured under either hypoxic (2.5% O 2 for 18 hours) ( N = 30) or normoxic (18% O 2 ) ( N = 30) conditions, then topically applied to the exposed cerebral cortex within 1 hour after traumatic brain injury. A thin layer of fibrin was used to fix the cells in position. No treatment was given to the animals with traumatic brain injury ( N = 30). Animals that underwent craniectomy without traumatic brain injury were treated as the sham group ( N = 15). Neurological functions were evaluated with water maze, Roto-rod and gait analysis. Animals were sacrificed at days 3, 7, and 14 for microscopic examinations and real-time polymerase chain reaction analysis. The rats treated with hypoxic mesenchymal stem cells showed the greatest improvement in neurological function recovery. More green fluorescent protein-positive cells were found in the injured brain parenchyma treated with hypoxic mesenchymal stem cells that co-expressed glial fibrillary acidic protein, Nestin, and NeuN. Moreover, there was early astrocytosis triggered by the infiltration of more glial fibrillary acidic protein-positive cells and microgliosis was suppressed with fewer ionized calcium binding adapter molecule 1-positive cells in the penumbra region of hypoxic mesenchymal stem cells group at day 3. Compared with normoxic mesenchymal stem cells and traumatic brain injury only groups, there was significantly ( p < 0.05) less neuronal death in both the hippocampus and penumbral regions in sections treated with hypoxic mesenchymal stem cells as determined by Cresyl violet and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining respectively. The expression of pro-inflammatory genes (interleukin 6, interleukin 1a, interleukin 1b, tumor necrosis factor α) was upregulated and apoptotic gene (Caspase-3) expression was suppressed at day 3. Anti-inflammatory (interleukin 10) and anti-apoptotic (BCL2 associated agonist of cell death) gene expression was upregulated at days 7 and 14. Our study showed that a hypoxic precondition enhanced the beneficial effects of mesenchymal stem cells on neurological recovery after traumatic brain injury. |
| first_indexed | 2024-12-11T05:10:00Z |
| format | Article |
| id | doaj.art-d0331c0101f54fd2af25f1f268aaa9cc |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-11T05:10:00Z |
| publishDate | 2019-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-d0331c0101f54fd2af25f1f268aaa9cc2022-12-22T01:19:56ZengSAGE PublishingCell Transplantation0963-68971555-38922019-07-012810.1177/0963689719855624The neuroprotection of hypoxic adipose tissue-derived mesenchymal stem cells in experimental traumatic brain injuryHui Ma0Ping Kuen Lam1Cindy See Wai Tong2Kin Ki Yan Lo3George Kwok Chu Wong4Wai Sang Poon5 Department of Surgery, Chow Tai Fook-Cheng Yu Tung Surgical Stem Cell Research Center, China Department of Surgery, Chow Tai Fook-Cheng Yu Tung Surgical Stem Cell Research Center, China Department of Surgery, The Chinese University of Hong Kong, China Department of Surgery, The Chinese University of Hong Kong, China Department of Surgery, Chow Tai Fook-Cheng Yu Tung Surgical Stem Cell Research Center, China Department of Surgery, Chow Tai Fook-Cheng Yu Tung Surgical Stem Cell Research Center, ChinaTraumatic brain injury is one of the leading causes of mortality and morbidity worldwide. At present there is no effective treatment. Previous studies have demonstrated that topical application of adipose tissue-derived mesenchymal stem cells can improve functional recovery in experimental traumatic brain injury. In this study, we evaluated whether hypoxic preconditioned mesenchymal stem cells could enhance the recovery from traumatic brain injury. Traumatic brain injury was induced with an electromagnetically controlled cortical impact device. Two million mesenchymal stem cells derived from the adipose tissue of transgenic green fluorescent protein Sprague-Dawley rats were cultured under either hypoxic (2.5% O 2 for 18 hours) ( N = 30) or normoxic (18% O 2 ) ( N = 30) conditions, then topically applied to the exposed cerebral cortex within 1 hour after traumatic brain injury. A thin layer of fibrin was used to fix the cells in position. No treatment was given to the animals with traumatic brain injury ( N = 30). Animals that underwent craniectomy without traumatic brain injury were treated as the sham group ( N = 15). Neurological functions were evaluated with water maze, Roto-rod and gait analysis. Animals were sacrificed at days 3, 7, and 14 for microscopic examinations and real-time polymerase chain reaction analysis. The rats treated with hypoxic mesenchymal stem cells showed the greatest improvement in neurological function recovery. More green fluorescent protein-positive cells were found in the injured brain parenchyma treated with hypoxic mesenchymal stem cells that co-expressed glial fibrillary acidic protein, Nestin, and NeuN. Moreover, there was early astrocytosis triggered by the infiltration of more glial fibrillary acidic protein-positive cells and microgliosis was suppressed with fewer ionized calcium binding adapter molecule 1-positive cells in the penumbra region of hypoxic mesenchymal stem cells group at day 3. Compared with normoxic mesenchymal stem cells and traumatic brain injury only groups, there was significantly ( p < 0.05) less neuronal death in both the hippocampus and penumbral regions in sections treated with hypoxic mesenchymal stem cells as determined by Cresyl violet and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining respectively. The expression of pro-inflammatory genes (interleukin 6, interleukin 1a, interleukin 1b, tumor necrosis factor α) was upregulated and apoptotic gene (Caspase-3) expression was suppressed at day 3. Anti-inflammatory (interleukin 10) and anti-apoptotic (BCL2 associated agonist of cell death) gene expression was upregulated at days 7 and 14. Our study showed that a hypoxic precondition enhanced the beneficial effects of mesenchymal stem cells on neurological recovery after traumatic brain injury.https://doi.org/10.1177/0963689719855624 |
| spellingShingle | Hui Ma Ping Kuen Lam Cindy See Wai Tong Kin Ki Yan Lo George Kwok Chu Wong Wai Sang Poon The neuroprotection of hypoxic adipose tissue-derived mesenchymal stem cells in experimental traumatic brain injury Cell Transplantation |
| title | The neuroprotection of hypoxic adipose tissue-derived mesenchymal stem cells in experimental traumatic brain injury |
| title_full | The neuroprotection of hypoxic adipose tissue-derived mesenchymal stem cells in experimental traumatic brain injury |
| title_fullStr | The neuroprotection of hypoxic adipose tissue-derived mesenchymal stem cells in experimental traumatic brain injury |
| title_full_unstemmed | The neuroprotection of hypoxic adipose tissue-derived mesenchymal stem cells in experimental traumatic brain injury |
| title_short | The neuroprotection of hypoxic adipose tissue-derived mesenchymal stem cells in experimental traumatic brain injury |
| title_sort | neuroprotection of hypoxic adipose tissue derived mesenchymal stem cells in experimental traumatic brain injury |
| url | https://doi.org/10.1177/0963689719855624 |
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