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Single-cell Analysis Reveals the Impact of Aging on Mesenchymal Stem Cells

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Review of “Single‐Cell Transcriptomics of Human Mesenchymal Stem Cells Reveal Age‐Related Cellular Subpopulation Depletion and Impaired Regenerative Function” from STEM CELLS by Stuart P. Atkinson 

The pro-regenerative properties of mesenchymal stem cells (MSCs) have promoted their widespread application in cell-based tissue-repair strategies; however, whether the natural aging process affects MSCs and their therapeutic output remains a contentious topic. While many failed to observe any adverse effects on MSC function, other groups have demonstrated diminished proliferation [1, 2], anti‐inflammatory activity [3], and multipotent differentiation potential [4] with increasing age.

Given these contrasting findings, researchers from the group of Geoffrey C. Gurtner (Stanford University, California, USA) looked to advances in microfluidic and molecular biology that allow the assessment of stem cell heterogeneity in the hope of defining the effect of aging on MSCs [5]. In their new STEM CELLS article, Khong et al. both establish that young donor MSCs promote wound healing at a faster rate than old donor MSCs and describe age-related transcriptional differences at the single-cell level [6].

Initial analyses of MSCs derived from young and old donors demonstrated no difference in metabolic activity, proliferation rates, or trilineage differentiation potential, in agreement with previous studies that found no link between aging and loss of function of MSCs. However, the authors subsequently discovered that young donor MSCs promoted more rapid and more robust wound repair in an in vivo mouse excisional wound model when compared to old donor MSCs. Through single‐cell transcriptomic analysis aided by microfluidics, the study linked enhanced wound healing observed to the higher expression of tissue regeneration-associated genes in a larger proportion of young MSCs with possibly enhanced stemness.

Overall, these data suggest that impaired wound healing by old donor MSCs may be due to a shift in subpopulation dynamics towards a larger proportion of cells expressing lower levels of critical genes and, therefore, displaying poor regenerative capabilities. The authors note several translational implications, including the possible ineffectiveness of autologous MSC therapy in elderly patients and the preference for young donors in allogeneic MSC therapy. 

For more on aging stem cells, single-cell analysis, and enhanced wound healing strategies, stay tuned to the Stem Cells Portal!

References

  1. Stolzing A, Jones E, McGonagle D, et al., Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies. Mechanisms of Ageing and Development 2008;129:163-173.
  2. Zaim M, Karaman S, Cetin G, et al., Donor age and long-term culture affect differentiation and proliferation of human bone marrow mesenchymal stem cells. Annals of Hematology 2012;91:1175-1186.
  3. Marędziak M, Marycz K, Tomaszewski KA, et al., The influence of aging on the regenerative potential of human adipose derived mesenchymal stem cells. STEM CELLS 2016;2016.
  4. Singh L, Brennan TA, Russell E, et al., Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage. Bone 2016;85:29-36.
  5. Januszyk M and Gurtner GC, High-Throughput Single-Cell Analysis for Wound Healing Applications. Advances in Wound Care 2013;2:457-469.
  6. Khong SML, Lee M, Kosaric N, et al., Single-Cell Transcriptomics of Human Mesenchymal Stem Cells Reveal Age-Related Cellular Subpopulation Depletion and Impaired Regenerative Function. STEM CELLS 2019;37:240-246.