Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph disease
Abstract Background Machado-Joseph disease is the most common autosomal dominant hereditary ataxia worldwide without effective treatment. Mesenchymal stem cells (MSCs) could slow the disease progression, but side effects limited their clinical application. Besides, MSC-derived exosomes exerted simil...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01727-2 |
| _version_ | 1818257493871034368 |
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| author | Hua-Jing You Shu-Bin Fang Teng-Teng Wu Hongyu Zhang Yu-Kun Feng Xue-Jiao Li Hui-Hua Yang Ge Li Xun-Hua Li Chao Wu Qing-Ling Fu Zhong Pei |
| author_facet | Hua-Jing You Shu-Bin Fang Teng-Teng Wu Hongyu Zhang Yu-Kun Feng Xue-Jiao Li Hui-Hua Yang Ge Li Xun-Hua Li Chao Wu Qing-Ling Fu Zhong Pei |
| author_sort | Hua-Jing You |
| collection | DOAJ |
| description | Abstract Background Machado-Joseph disease is the most common autosomal dominant hereditary ataxia worldwide without effective treatment. Mesenchymal stem cells (MSCs) could slow the disease progression, but side effects limited their clinical application. Besides, MSC-derived exosomes exerted similar efficacy and have many advantages over MSCs. The aim of this study was to examine the efficacy of MSC-derived exosomes in YACMJD84.2 mice. Methods Rotarod performance was evaluated every 2 weeks after a presymptomatic administration of intravenous MSC-derived exosomes twice in YACMJD84.2 mice. Loss of Purkinje cells, relative expression level of Bcl-2/Bax, cerebellar myelin loss, and neuroinflammation were assessed 8 weeks following treatment. Results MSC-derived exosomes were isolated and purified through anion exchange chromatography. Better coordination in rotarod performance was maintained for 6 weeks in YACMJD84.2 mice with exosomal treatment, compared with those without exosomal treatment. Neuropathological changes including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation were also attenuated 8 weeks after exosomal treatment. The higher relative ratio of Bcl-2/Bax was consistent with the attenuation of loss of Purkinje cells. Conclusions MSC-derived exosomes could promote rotarod performance and attenuate neuropathology, including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation. Therefore, MSC-derived exosomes have a great potential in the treatment of Machado-Joseph disease. |
| first_indexed | 2024-12-12T17:44:32Z |
| format | Article |
| id | doaj.art-96d14b6cc80440e0a2486c52bfb1074b |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-12T17:44:32Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-96d14b6cc80440e0a2486c52bfb1074b2022-12-22T00:16:58ZengBMCStem Cell Research & Therapy1757-65122020-06-0111111110.1186/s13287-020-01727-2Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph diseaseHua-Jing You0Shu-Bin Fang1Teng-Teng Wu2Hongyu Zhang3Yu-Kun Feng4Xue-Jiao Li5Hui-Hua Yang6Ge Li7Xun-Hua Li8Chao Wu9Qing-Ling Fu10Zhong Pei11Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of NeurologyOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of NeurologyOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Neurology, The Fifth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring InstituteDepartment of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of NeurologyGuangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring InstituteDepartment of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of NeurologyDepartment of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of NeurologyOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of NeurologyAbstract Background Machado-Joseph disease is the most common autosomal dominant hereditary ataxia worldwide without effective treatment. Mesenchymal stem cells (MSCs) could slow the disease progression, but side effects limited their clinical application. Besides, MSC-derived exosomes exerted similar efficacy and have many advantages over MSCs. The aim of this study was to examine the efficacy of MSC-derived exosomes in YACMJD84.2 mice. Methods Rotarod performance was evaluated every 2 weeks after a presymptomatic administration of intravenous MSC-derived exosomes twice in YACMJD84.2 mice. Loss of Purkinje cells, relative expression level of Bcl-2/Bax, cerebellar myelin loss, and neuroinflammation were assessed 8 weeks following treatment. Results MSC-derived exosomes were isolated and purified through anion exchange chromatography. Better coordination in rotarod performance was maintained for 6 weeks in YACMJD84.2 mice with exosomal treatment, compared with those without exosomal treatment. Neuropathological changes including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation were also attenuated 8 weeks after exosomal treatment. The higher relative ratio of Bcl-2/Bax was consistent with the attenuation of loss of Purkinje cells. Conclusions MSC-derived exosomes could promote rotarod performance and attenuate neuropathology, including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation. Therefore, MSC-derived exosomes have a great potential in the treatment of Machado-Joseph disease.http://link.springer.com/article/10.1186/s13287-020-01727-2Machado-Joseph diseaseMesenchymal stem cell-derived exosomesMotor functionNeuropathology |
| spellingShingle | Hua-Jing You Shu-Bin Fang Teng-Teng Wu Hongyu Zhang Yu-Kun Feng Xue-Jiao Li Hui-Hua Yang Ge Li Xun-Hua Li Chao Wu Qing-Ling Fu Zhong Pei Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph disease Stem Cell Research & Therapy Machado-Joseph disease Mesenchymal stem cell-derived exosomes Motor function Neuropathology |
| title | Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph disease |
| title_full | Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph disease |
| title_fullStr | Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph disease |
| title_full_unstemmed | Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph disease |
| title_short | Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph disease |
| title_sort | mesenchymal stem cell derived exosomes improve motor function and attenuate neuropathology in a mouse model of machado joseph disease |
| topic | Machado-Joseph disease Mesenchymal stem cell-derived exosomes Motor function Neuropathology |
| url | http://link.springer.com/article/10.1186/s13287-020-01727-2 |
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