Mesenchymal stem cell-derived extracellular vesicles reduce senescence and extend health span in mouse models of aging.

Autor: Dorronsoro A; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA., Santiago FE; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA.; Institute on the Biology of Aging and Metabolism and Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA., Grassi D; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA., Zhang T; Institute on the Biology of Aging and Metabolism and Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA., Lai RC; Institute of Medical Biology, ASTAR, Singapore, Singapore., McGowan SJ; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA.; Institute on the Biology of Aging and Metabolism and Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA., Angelini L; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA.; Institute on the Biology of Aging and Metabolism and Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA., Lavasani M; The Shirley Ryan AbilityLab, Chicago, Illinois, USA., Corbo L; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA., Lu A; The Steadman Philippon Research Institute, Vail, Colorado, USA., Brooks RW; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA., Garcia-Contreras M; Diabetes Research Institute, University of Miami, Miami, Florida, USA., Stolz DB; Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylveniya, USA., Amelio A; Lineberger Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.; Department of Bioinformatics, Scripps Research, Jupiter, Florida, USA., Boregowda SV; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA., Fallahi M; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA.; Department of Bioinformatics, Scripps Research, Jupiter, Florida, USA., Reich A; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA.; Department of Bioinformatics, Scripps Research, Jupiter, Florida, USA., Ricordi C; Diabetes Research Institute, University of Miami, Miami, Florida, USA., Phinney DG; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA., Huard J; The Steadman Philippon Research Institute, Vail, Colorado, USA., Lim SK; Institute of Medical Biology, ASTAR, Singapore, Singapore., Niedernhofer LJ; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA.; Institute on the Biology of Aging and Metabolism and Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA., Robbins PD; Center on Aging and Departments of Molecular Medicine, Scripps Research, Jupiter, Florida, USA.; Institute on the Biology of Aging and Metabolism and Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2021 Apr; Vol. 20 (4), pp. e13337. Date of Electronic Publication: 2021 Mar 16.
DOI: 10.1111/acel.13337
Abstrakt: Aging drives progressive loss of the ability of tissues to recover from stress, partly through loss of somatic stem cell function and increased senescent burden. We demonstrate that bone marrow-derived mesenchymal stem cells (BM-MSCs) rapidly senescence and become dysfunctional in culture. Injection of BM-MSCs from young mice prolonged life span and health span, and conditioned media (CM) from young BM-MSCs rescued the function of aged stem cells and senescent fibroblasts. Extracellular vesicles (EVs) from young BM-MSC CM extended life span of Ercc1 -/- mice similarly to injection of young BM-MSCs. Finally, treatment with EVs from MSCs generated from human ES cells reduced senescence in culture and in vivo, and improved health span. Thus, MSC EVs represent an effective and safe approach for conferring the therapeutic effects of adult stem cells, avoiding the risks of tumor development and donor cell rejection. These results demonstrate that MSC-derived EVs are highly effective senotherapeutics, slowing the progression of aging, and diseases driven by cellular senescence.
(© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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