Extracellular vesicles deposit PCNA to rejuvenate aged bone marrow–derived mesenchymal stem cells and slow age-related degeneration
| Autor: | Teng Liu, Qiong Zhang, Li Chen, Qiubai Li, Zhichao Chen, Qian Lei, Wenxiang Ren, Shaojun Guo, An-Yuan Guo, Wenlan Chen, Yulin Cao, Fei Gao, Hongxiang Wang, Weiqun Chen, Yu Hu |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Science Translational Medicine. 13 |
| ISSN: | 1946-6242 1946-6234 |
| Popis: | Stem cell senescence increases alongside the progressive functional declines that characterize aging. The effects of extracellular vesicles (EVs) are now attracting intense interest in the context of aging and age-related diseases. Here, we demonstrate that neonatal umbilical cord (UC) is a source of EVs derived from mesenchymal stem cells (MSC-EVs). These UC-produced MSC-EVs (UC-EVs) contain abundant anti-aging signals and rejuvenate senescing adult bone marrow-derived MSCs (AB-MSCs). UC-EV-rejuvenated AB-MSCs exhibited alleviated aging phenotypes and increased self-renewal capacity and telomere length. Mechanistically, UC-EVs rejuvenate AB-MSCs at least partially by transferring proliferating cell nuclear antigen (PCNA) into recipient AB-MSCs. When tested in therapeutic context, UC-EV-triggered rejuvenation enhanced the regenerative capacities of AB-MSCs in bone formation, wound healing, and angiogenesis. Intravenously injected UC-EVs conferred anti-aging phenotypes including decreased bone and kidney degeneration in aged mice. Our findings reveal that UC-EVs are of high translational value in anti-aging intervention. |
| Databáze: | OpenAIRE |
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