Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy
Abstract Background and aims Refractory epilepsy is also known as drug-resistant epilepsy with limited clinical treatment. Benefitting from its safety and easy availability, olfactory mucosa mesenchymal stem cells (OM-MSCs) are considered a preferable MSC source for clinical application. This study...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-023-03458-6 |
| _version_ | 1797453712684220416 |
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| author | Zheng-Zhao Liu Yan Huang Chun-Gu Hong Xin Wang Ran Duan Jian-Yang Liu Jia-Lin He Da Duan Hui Xie Ming Lu |
| author_facet | Zheng-Zhao Liu Yan Huang Chun-Gu Hong Xin Wang Ran Duan Jian-Yang Liu Jia-Lin He Da Duan Hui Xie Ming Lu |
| author_sort | Zheng-Zhao Liu |
| collection | DOAJ |
| description | Abstract Background and aims Refractory epilepsy is also known as drug-resistant epilepsy with limited clinical treatment. Benefitting from its safety and easy availability, olfactory mucosa mesenchymal stem cells (OM-MSCs) are considered a preferable MSC source for clinical application. This study aims to investigate whether OM-MSCs are a promising alternative source for treating refractory epilepsy clinically and uncover the mechanism by OM-MSCs administration on an epileptic mouse model. Methods OM-MSCs were isolated from turbinal and characterized by flow cytometry. Autologous human OM-MSCs treatment on a patient was carried out using intrathecal administration. Epileptic mouse model was established by 1 mg/kg scopolamine and 300 mg/kg pilocarpine treatment (intraperitoneal). Stereotaxic microinjection was employed to deliver the mouse OM-MSCs. Mouse electroencephalograph recording was used to investigate the seizures. Brain structure was evaluated by magnetic resonance imaging (MRI). Immunohistochemical and immunofluorescent staining of GFAP, IBA1, MAP2, TUBB3, OLIG2, CD4, CD25, and FOXP3 was carried out to investigate the neural cells and Treg cells. QRT-PCR and ELISA were performed to determine the cytokines (Il1b, Il6, Tnf, Il10) on mRNA and protein level. Y-maze, the object location test, and novel object recognition test were performed to measure the cognitive function. Footprint test, rotarod test, balance beam test, and grip strength test were conducted to evaluate the locomotive function. Von Frey testing was carried out to assess the mechanical allodynia. Results Many beneficial effects of the OM-MSC treatment on disease status, including seizure type, frequency, severity, duration, and cognitive function, and no apparent adverse effects were observed at the 8-year follow-up case. Brain MRI indicated that autologous OM-MSC treatment alleviated brain atrophy in epilepsy patients. A study in an epileptic mouse model revealed that OM-MSC treatment recruited Treg cells to the brain, inhibited inflammation, rebuilt the neural network, and improved the cognitive, locomotive, and perceptive functions of epileptic mice. Conclusions Autologous OM-MSC treatment is efficacious for improving chronic refractory epilepsy, suggesting a future therapeutic candidate for epilepsy. Trial registration: The study was registered with Chinese Clinical Trial Registry (ChiCTR2200055357). |
| first_indexed | 2024-03-09T15:26:45Z |
| format | Article |
| id | doaj.art-e09a702e43d44f3f8e5aa9f38e1ae180 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-09T15:26:45Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-e09a702e43d44f3f8e5aa9f38e1ae1802023-11-26T12:31:03ZengBMCStem Cell Research & Therapy1757-65122023-09-0114111610.1186/s13287-023-03458-6Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsyZheng-Zhao Liu0Yan Huang1Chun-Gu Hong2Xin Wang3Ran Duan4Jian-Yang Liu5Jia-Lin He6Da Duan7Hui Xie8Ming Lu9Department of Orthopedics, Xiangya Hospital, Central South UniversityNHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care HospitalMovement System Injury and Repair Research Center, Xiangya Hospital, Central South UniversityMovement System Injury and Repair Research Center, Xiangya Hospital, Central South UniversityMovement System Injury and Repair Research Center, Xiangya Hospital, Central South UniversityDepartment of Neurology, The Second Xiangya Hospital, Central South UniversityDepartment of Neurology, The Second Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, the 921st Hospital of PLA (Second Affiliated Hospital of Hunan Normal University)Department of Orthopedics, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, the 921st Hospital of PLA (Second Affiliated Hospital of Hunan Normal University)Abstract Background and aims Refractory epilepsy is also known as drug-resistant epilepsy with limited clinical treatment. Benefitting from its safety and easy availability, olfactory mucosa mesenchymal stem cells (OM-MSCs) are considered a preferable MSC source for clinical application. This study aims to investigate whether OM-MSCs are a promising alternative source for treating refractory epilepsy clinically and uncover the mechanism by OM-MSCs administration on an epileptic mouse model. Methods OM-MSCs were isolated from turbinal and characterized by flow cytometry. Autologous human OM-MSCs treatment on a patient was carried out using intrathecal administration. Epileptic mouse model was established by 1 mg/kg scopolamine and 300 mg/kg pilocarpine treatment (intraperitoneal). Stereotaxic microinjection was employed to deliver the mouse OM-MSCs. Mouse electroencephalograph recording was used to investigate the seizures. Brain structure was evaluated by magnetic resonance imaging (MRI). Immunohistochemical and immunofluorescent staining of GFAP, IBA1, MAP2, TUBB3, OLIG2, CD4, CD25, and FOXP3 was carried out to investigate the neural cells and Treg cells. QRT-PCR and ELISA were performed to determine the cytokines (Il1b, Il6, Tnf, Il10) on mRNA and protein level. Y-maze, the object location test, and novel object recognition test were performed to measure the cognitive function. Footprint test, rotarod test, balance beam test, and grip strength test were conducted to evaluate the locomotive function. Von Frey testing was carried out to assess the mechanical allodynia. Results Many beneficial effects of the OM-MSC treatment on disease status, including seizure type, frequency, severity, duration, and cognitive function, and no apparent adverse effects were observed at the 8-year follow-up case. Brain MRI indicated that autologous OM-MSC treatment alleviated brain atrophy in epilepsy patients. A study in an epileptic mouse model revealed that OM-MSC treatment recruited Treg cells to the brain, inhibited inflammation, rebuilt the neural network, and improved the cognitive, locomotive, and perceptive functions of epileptic mice. Conclusions Autologous OM-MSC treatment is efficacious for improving chronic refractory epilepsy, suggesting a future therapeutic candidate for epilepsy. Trial registration: The study was registered with Chinese Clinical Trial Registry (ChiCTR2200055357).https://doi.org/10.1186/s13287-023-03458-6Autologous transplantOlfactory mucosa mesenchymal stem cellRefractory epilepsyDiffusion cerebral atrophyTreg cellsInflammation |
| spellingShingle | Zheng-Zhao Liu Yan Huang Chun-Gu Hong Xin Wang Ran Duan Jian-Yang Liu Jia-Lin He Da Duan Hui Xie Ming Lu Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy Stem Cell Research & Therapy Autologous transplant Olfactory mucosa mesenchymal stem cell Refractory epilepsy Diffusion cerebral atrophy Treg cells Inflammation |
| title | Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy |
| title_full | Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy |
| title_fullStr | Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy |
| title_full_unstemmed | Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy |
| title_short | Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy |
| title_sort | autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy |
| topic | Autologous transplant Olfactory mucosa mesenchymal stem cell Refractory epilepsy Diffusion cerebral atrophy Treg cells Inflammation |
| url | https://doi.org/10.1186/s13287-023-03458-6 |
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