Single-Cell Transcriptomics of Human Mesenchymal Stem Cells Reveal Age-Related Cellular Subpopulation Depletion and Impaired Regenerative Function

Stem Cells. 2019 Feb;37(2):240-246. doi: 10.1002/stem.2934. Epub 2018 Nov 9.

Abstract

Although bone marrow-derived mesenchymal stem cells (BM-MSCs) are widely recognized as promising therapeutic agents, the age-related impacts on cellular function remain largely uncharacterized. In this study, we found that BM-MSCs from young donors healed wounds in a xenograft model faster compared with their aged counterparts (p < .001). Given this significant healing advantage, we then used single-cell transcriptomic analysis to provide potential molecular insights into these observations. We found that the young cells contained a higher proportion of cells characterized by a higher expression of genes involved in tissue regeneration. In addition, we identified a unique, quiescent subpopulation that was exclusively present in young donor cells. Together, these findings may explain a novel mechanism for the enhanced healing capacity of young stem cells and may have implications for autologous cell therapy in the extremes of age. Stem Cells 2019;37:240-246.

Keywords: Aging; Mesenchymal stem cells; Regeneration; Subpopulation; Therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aging
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cellular Senescence
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Transcriptome / genetics*
  • Young Adult