STEM CELLS | 2019
Young Versus Adult: Finding Clues to Unravel the Increased Regenerative Ability of Stem Cells from Young Donors
Abstract
With great interest, I have read the manuscript by Khong et al. [1], in which they describe the possible impact of age-related effects on the regenerative ability of bone marrow-derived mesenchymal stem cells (BM-MSCs). In this study, they indeed conclude that BM-MSCs from young donors heal wounds in a xenograft model faster compared with their aged counterparts. Intriguingly, by using a microfluidic-based single cell transcriptomic analysis, they identified a BM-MSC subpopulation cluster that contained more young BM-MSCs. Analytical methods were used to compare gene expression patterns related to tissue regeneration in this cluster. Interestingly, the young population of cells exhibited only a mildly increased gene signature favoring tissue regeneration. This mildly increased gene expression could not fully explain the striking difference in wound healing between the young and aged BM-MSCs. Therefore, t-Stochastic Neighbor Embedding was applied and a subpopulation with overall diminished gene expression but specifically with respect to tissue regeneration was identified among the young BM-MSC population only. Therefore, the authors concluded that the enhanced wound healing ability of young BMCs must be caused by a combination of a pro-regenerative phenotype with a presence of a pool of quiescent MSCs, only present among the young BMMSCs, with increased stemness. In 2011, our group published a manuscript on the difference in cardiac differentiation ability of young versus adult donor derived MSCs [2]. In this study, we compared human embryonic derived MSCs to MSCs derived from different fetal tissues and adult tissues. In accordance to the manuscript of Khong et al. [1], we also found a reduced regenerative ability with increasing donor age. In our study, the MSCs derived from aged donors were not able to differentiate toward any of the cardiac cell types. To explain the difference in regenerative capacity, we hypothesized that this could be caused by the existence of a subpopulation among the MSCs derived from the young donors. It is, therefore, very interesting to read the study by Khong et al. [1], in which they find a subpopulation among the young BM-MSCs with a pro-regenerative phenotype. In the discussion, they suggest future studies, in addition to those studies, it could be of importance to select the subpopulation of young BM-MSCs with the pro-regenerative capacity and the quiescent MSCs and investigate their wound healing abilities. Additionally, it would be very interesting to repeat these experiments using MSCs from even younger donors in future experiments. Khong et al. [1] stated that their findings may have implications for autologous cell therapy in the elderly. In the field of cardiac regeneration, however, clinical trials have been conducted using allogeneic stem cells proving their safety [3]. These findings in combination of those of the study by Khong et al. [1] could lead to an improved strategy in regenerative medicine by specifically selecting the subpopulation MSCs from young donors for therapeutic purposes.