Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph disease

Autor: Chao Wu, Huajing You, Zhong Pei, Xue‐jiao Li, Hui-Hua Yang, Hong-Yu Zhang, Qing-Ling Fu, Yukun Feng, Tengteng Wu, Xunhua Li, Shu-Bin Fang, Ge Li
Rok vydání: 2020
Předmět:
Zdroj: Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-11 (2020)
Stem Cell Research & Therapy
ISSN: 1757-6512
DOI: 10.1186/s13287-020-01727-2
Popis: 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.
Databáze: OpenAIRE
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