Research ArticleStem Cells

Extracellular vesicles deposit PCNA to rejuvenate aged bone marrow–derived mesenchymal stem cells and slow age-related degeneration

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Science Translational Medicine  27 Jan 2021:
Vol. 13, Issue 578, eaaz8697
DOI: 10.1126/scitranslmed.aaz8697

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Decelerating degeneration

Mesenchymal stem cells (MSCs) have been used for tissue repair and regeneration, but the regenerative potential of the cells declines with aging. Lei et al. found that extracellular vesicles (EVs) from neonatal human umbilical cord MSCs (UC-EVs) could rejuvenate senescent adult MSCs derived from bone marrow. In mouse models, UC-EVs improved skin wound repair, decreased oxidative stress, and reduced aging-related markers in different organs. The authors identified the transfer of PCNA from UC-EVs to MSCs as a potential mechanism responsible for the rejuvenation. Results illustrate how treatment with UC-EVs could help combat aging-related degeneration.

Abstract

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.

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