Extracellular vesicles from human stem cells can alleviate cellular aging in culture

Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communications and exert various biological activities via delivering unique cargos of functional molecules such as proteins to recipient cells. Previous studies showed that EVs produced and secreted by human mesenchymal stem cells (MSCs) can substitute intact MSCs for tissue repair and regeneration.

In this study, researchers from Johns Hopkins University School of Medicine examined properties and functions of EVs from human induced pluripotent stem cells (iPSCs) that can be cultured infinitely under a chemically defined medium free of any exogenous EVs. The researchers collected and purified EVs secreted by human iPSCs and MSCs. Purified EVs produced by both stem cell types have similar sizes (~150 nm in diameter), but human iPSCs produced 16-fold more EVs than MSCs. When highly purified iPSC-EVs were applied in culture to senescent MSCs that have elevated reactive oxygen species (ROS), they reduced cellular ROS levels and alleviated aging phenotypes of senescent MSCs. This discovery reveals that EVs from human stem cells can alleviate cellular aging in culture, at least in part by delivering intracellular peroxiredoxin antioxidant enzymes.

Uptake of W5 and effects on the growth of recipient cells


(A) Time—course analysis of uptake of PKH26 red fluorescent dye‐labelled iPSC‐EVs and MSC‐EVs by MSCs. Scale bar, 50 p.m. (b) Representative images of BC1—EV and BC1‐MSC—EV uptake by MSCS after PKH26 red fluorescent dye labeling. Scale bar, 50 μm. (C) Quantification of PKH26 staining on MSCs. (D) Quantification of DAPI staining in MSCS. (E) Measurements of labeling efficiency of iPSC‐Evs and MSC‐EVs by PKH26 red fluorescent dye. (F) AlamarBlue assay to assess the cell growth of early‐passage MSCs (p3‐p5) after incubation with iPSC‐EVs or MSC‐EVs. (G) AlamarBlue assay to assess the cell growth of early‐passage HUVECs (p4‐p7) after incubation with iPSC‐EVs or MSC‐EVs. All data reflect mean ± SD from 3 independent experiments. ns, not significant; **p < .01.

Liu S, Mahairaki V, Bai H, Ding Z, Li J, Witwer KW, Cheng L. (2019) Highly purified human extracellular vesicles produced by stem cells alleviate aging cellular phenotypes of senescent human cells. Stem Cells [Epub ahead of print]. [abstract]

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