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

• Published in: Stem cells (Dayton, Ohio) Vol. 37; no. 2; pp. 240 - 246
• Main Authors: Khong, Sacha M. L., Lee, Ming, Kosaric, Nina, Khong, Danika M., Dong, Yixiao, Hopfner, Ursula, Aitzetmüller, Matthias M., Duscher, Dominik, Schäfer, Richard, Gurtner, Geoffrey C.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.02.2019; Oxford University Press
• Subjects: Adult; Age; Aged; Aging; Animals; Autografts; Bone marrow; Cell Differentiation; Cell Proliferation; Cellular Senescence; Chemical compounds; Depletion; Gene expression; Healing; Humans; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; Pharmacology; Regeneration; Stem cells; Subpopulation; Therapy; Tissue engineering; Transcriptome - genetics; Xenografts; Xenotransplantation; Young Adult; Aging; Regeneration; Therapy; Subpopulation; Mesenchymal stem cells
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.2934

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 BM‐MSCs from young donors healed wounds in a xenograft model faster compared with their aged counterparts. 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 suggest distinct “cluster signatures” of MSCs as a possible approach on how to classify potent MSC preparations.