| Autor: |
Yi-Chen Huang, Tsung-Jung Ho, Zhen-Xiang Hong, Tzyy-Wen Chiou, Hsueh-Hui Yang, Hui-Xuan Zheng, Pei-Yu Chen, Horng-Jyh Harn, Yu-Shuan Chen, Yi-Tung Lin, Lin Shinn-Zong, Hsieh-Chih Tsai, Peir-Rong Chen |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.21203/rs.3.rs-820726/v1 |
| Popis: |
Background The development of acellular products is a new trend for regeneration medicine. To provide an acellular product exhibiting characteristics of cells and usefulness as a therapeutic agent, exosomes were employed in the current studies. Method and Result The therapeutic agent hsa-miRNA-6780-5p was enriched up to 98 folds in exosomes derived from butylidenephthalide (bdph)-pre-conditioned human olfactory ensheathing cells (hOECs) compared to naïve hOECs exosomes. The particle size of exosomes derived hOECs and exosomes derived hOECs pre-conditioned bdph were around 124.17 nm and 117.47 nm, respectively. The role of hsa-miRNA-6780-5p was first demonstrated in our studies using a liposome system, showing that it enhances autophagy and inhibits spinocerebellar ataxia type 3 (SCA3) disease proteins of polyglutamine (polyQ) tract expression. At the same time, the exosomes with enriched hsa-miRNA-6780-5p were further applied to HEK-293-84Q, thus resulting in decreased expressions of polyQ and increased autophagy in the cells. In contrast, the results were reversed when the autophagy inhibitor, 3MA, was added to the cells treated with hsa-miRNA-6780-5p enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. The SCA3 mice showed improved motor coordination behavior when they received intracranially injected exosomes enriched with hsa-miRNA-6780-5p. The SCA3 mouse cerebellum tissue having received hsa-miRNA6780-5p enriched exosomes also showed a decreased expression of polyQ and increased expression of autophagy marker. Conclusions Together, our findings provide an alternative therapeutic strategy for SCA3 disease treatment, using miRNA enriched exosomes derived from chemically pre-conditioned cells. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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