دورية أكاديمية
Administration of AG490 decreases the senescence of umbilical cord-mesenchymal stem cells and promotes the cytotherapeutic effect in liver fibrosis
| العنوان: | Administration of AG490 decreases the senescence of umbilical cord-mesenchymal stem cells and promotes the cytotherapeutic effect in liver fibrosis |
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| المؤلفون: | Chenhao Jiang, Huaxin Chen, Yinqian Kang, Xinyi He, Jianyang Huang, Tongyu Lu, Xin Sui, Haitian Chen, Jiaqi Xiao, Jiebin Zhang, Hanwen Zhang, Jun Zheng, Yang Yang, Jia Yao, Jianye Cai, Yingcai Zhang |
| المصدر: | Cell Death Discovery, Vol 9, Iss 1, Pp 1-10 (2023) |
| بيانات النشر: | Nature Publishing Group, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens LCC:Cytology |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671 |
| الوصف: | Abstract The therapeutic potential of umbilical cord-mesenchymal stem cell (UC-MSC) transplantation in liver fibrosis has been highlighted. However, the fate of transplanted MSCs in the fibrotic microenvironment remains unclear. In this study, we aim to uncover the fate of transplanted MSCs and develop targeting strategies that could enhance the therapeutic efficacy of MSC therapy in liver fibrosis. We used human UC-MSCs as the study object. For in vitro experiments, we stimulated UC-MSCs with several fibrotic-related factors (Liver fibrotic Factors, LF), including TGFβ, TNFα and IFNγ for downstream investigations. We co-cultured LF-treated UC-MSCs with hepatic stellate cell line LX-2 to assess the anti-fibrotic effect. We showed that upon LF stimulation, UC-MSCs exhibited reduced anti-fibrotic activity and underwent rapid senescence. Pathway analysis showed that JAK/STAT3 signaling was highly activated upon LF stimulation, which significantly elevated senescence-associated secretory phenotype (SASP) and senescence in UC-MSCs and could be reversed by a specific JAK inhibitor AG490. Moreover, using both carbon tetrachloride (CCl4) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induce fibrosis models, we demonstrated that AG490 pretreatment promoted UC-MSCs survival within the fibrotic liver microenvironment and exhibited enhance therapeutic efficacy. Overall, we showed that targeting MSC senescence in vivo through AG490 pretreatment could enhance the anti-fibrotic activities of UC-MSCs. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2058-7716 |
| Relation: | https://doaj.org/toc/2058-7716 |
| DOI: | 10.1038/s41420-023-01546-3 |
| URL الوصول: | https://doaj.org/article/7754c39d7fae4450aa36183a1f3f34cd |
| رقم الأكسشن: | edsdoj.7754c39d7fae4450aa36183a1f3f34cd |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20587716 |
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| DOI: | 10.1038/s41420-023-01546-3 |