@article{409187c759f1443ab022fd85bd96821d,
title = "Highly Purified Human Extracellular Vesicles Produced by Stem Cells Alleviate Aging Cellular Phenotypes of Senescent Human Cells",
abstract = "Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communications and exert various biological activities via delivering unique cargos of functional molecules such as RNAs and 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, we 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. We 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), human iPSC-EVs reduced cellular ROS levels and alleviated aging phenotypes of senescent MSCs. Our discovery reveals that EVs from human stem cells can alleviate cellular aging in culture, at least in part by delivering intracellular peroxiredoxin antioxidant enzymes. Stem Cells 2019;37:779–790.",
keywords = "Aging, Extracellular vesicles, Human induced pluripotent stem cells, Mesenchymal stem cells, Peroxiredoxin, Senescence",
author = "Senquan Liu and Vasiliki Mahairaki and Hao Bai and Zheng Ding and Jiaxin Li and Witwer, {Kenneth W.} and Linzhao Cheng",
note = "Funding Information: We thank Dr. Nicole Noren Hooten in NIA for suggestions for assays of cellular senescence phenotypes, Dr. David Clark, and Dr. Hui Zhang in Johns Hopkins' Mass Spectrometry Core Facility in the Center for Biomarker Discovery and Translation for proving expert proteomic analysis of purified EVs. This study was supported in part by grants from Maryland Stem Cell Research Fund (2016-MSCRFE-2739 and 2017-MSCRFD-3861) and National Institutes of Health (R56 AG-057430). L.C. is the Lucas and Lynn Chair of Hematology in the Johns Hopkins University. Funding Information: We thank Dr. Nicole Noren Hooten in NIA for suggestions for assays of cellular senescence phenotypes, Dr. David Clark, and Dr. Hui Zhang in Johns Hopkins{\textquoteright} Mass Spectrometry Core Facility in the Center for Biomarker Discovery and Translation for proving expert proteomic analysis of purified EVs. This study was supported in part by grants from Maryland Stem Cell Research Fund (2016-MSCRFE-2739 and 2017-MSCRFD-3861) and National Institutes of Health (R56 AG-057430). L.C. is the Lucas and Lynn Chair of Hematology in the Johns Hopkins University. Publisher Copyright: {\textcopyright}2019 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2019",
year = "2019",
month = jun,
doi = "10.1002/stem.2996",
language = "English (US)",
volume = "37",
pages = "779--790",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "6",
}