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

Akaitz Dorronsoro, Fernando E. Santiago, Diego Grassi, Tianpeng Zhang, Ruenn Chai Lai, Sara J. McGowan, Luise Angelini, Mitra Lavasani, Lana Corbo, Aiping Lu, Robert W. Brooks, Marta Garcia-Contreras, Donna B. Stolz, Antonio Amelio, Siddaraju V. Boregowda, Mohammad Fallahi, Adrian Reich, Camillo Ricordi, Donald G. Phinney, Johnny HuardSai Kiang Lim, Laura J. Niedernhofer, Paul D. Robbins

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere13337
JournalAging Cell
Volume20
Issue number4
DOIs
StatePublished - Apr 2021
Externally publishedYes

Keywords

  • aging
  • extracellular vesicles
  • mesenchymal stem cells
  • senescence
  • stem cells

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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