Modifiers of mesenchymal stem cell quantity and quality.

Abstract

Clinical trials involving mesenchymal stem cell (MSC) therapy have variable outcomes. We hypothesize this is largely attributed to donor-to-donor variability and tissue of origin. We examined proliferation rates, cytokine secretion profiles, and differentiation capability of seven bone marrow-derived MSCs (BM-MSCs) and 16 adipose tissue-derived MSCs (AD-MSCs) from 23 donors. AD-MSCs had the capacity to undergo more than 40 population doublings, while the BM-MSC proliferation rate was found to be considerably slower. We observed more donor-to-donor variability in proliferation rates of BM-MSCs than with AD-MSCs. Cytokine analysis revealed that secretion of eight cytokines was significantly increased by AD-MSCs at Passage (P)3 compared with P1, while for BM-MSCs at P3 relative to P1, only interleukin-8 and RANTES secretion was significantly increased. By P5, secretion of all cytokines by AD-MSCs was either decreased or unchanged relative to P1. In contrast, cytokine secretion by BM-MSCs at P5 was mostly unchanged, although secretion of six cytokines was significantly increased relative to P1. When we compared cytokine secretion between AD-MSCs and BM-MSCs at P3, AD-MSCs significantly secreted higher concentrations of cytokines than BM-MSCs while the opposite was observed at P5. This suggests that BM-MSCs are relatively more potent at P5 while AD-MSCs are relatively more potent at P3. AD-MSCs and BM-MSCs exhibited the capacity for chondrogenic differentiation. AD-MSCs and BM-MSCs appeared to display a more enhanced inclination toward adipogenic and osteogenic differentiation, respectively. MSC physiology is significantly influenced by donor variability and tissue of origin and this should be considered when designing clinical trials.