Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells
| Autor: | Zhongchao Han, Jia Xu, Lingling Wang, Deling Kong, Zongjin Li, Qian Ji, Na Liu, Yan Zhang, Siying Liu, Kaiyue Zhang, Meikuang Lim, Kaige Cui, Shuang Zhao |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Embryonic stem cells IGF1/PI3K/AKT pathway Cell Cell- and Tissue-Based Therapy Medicine (miscellaneous) Biology Cellular senescence Mesenchymal Stem Cell Transplantation Regenerative medicine Cell therapy Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Insulin-Like Growth Factor I Pharmacology Toxicology and Pharmaceutics (miscellaneous) PI3K/AKT/mTOR pathway Mice Inbred BALB C Mesenchymal stem cell Mesenchymal Stem Cells Extracellular vesicles Embryonic stem cell In vitro Cell biology Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Wounds and Injuries Immunostaining Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Background: Embryonic stem cells (ES) have a great potential for cell-based therapies in a regenerative medicine. However, the ethical and safety issues limit its clinical application. ES-derived extracellular vesicles (ES-EVs) have been reported suppress cellular senescence. Mesenchymal stem cells (MSCs) are widely used for clinical cell therapy. In this study, we investigated the beneficial effects of ES-EVs on aging MSCs to further enhancing their therapeutic effects. Methods: In vitro, we explored the rejuvenating effects of ES-EVs on senescent MSCs by senescence-associated β-gal (SA-β-gal) staining, immunostaining, and DNA damage foci analysis. The therapeutic effect of senescent MSC pre-treated with ES-EVs was also evaluated by using mouse cutaneous wound model. Results: We found that ES-EVs significantly rejuvenated the senescent MSCs in vitro and improve the therapeutic effects of MSCs in a mouse cutaneous wound model. In addition, we also identified that the IGF1/PI3K/AKT pathway mediated the antisenescence effects of ES-EVs on MSCs. Conclusions: Our results suggested that ES cells derived-extracellular vesicles possess the antisenescence properties, which significantly rejuvenate the senescent MSCs and enhance the therapeutic effects of MSCs. This strategy might emerge as a novel therapeutic strategy for MSCs clinical application. |
| Databáze: | OpenAIRE |
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