Mesenchymal Stem/Stromal Cells (MSCs) from Mouse Pelvic vs. Long Bones Exhibit Disparate Critical Quality Attributes: Implications for Translational Studies

Mesenchymal stem/stromal cells (MSCs) have been exploited as an experimental cell therapy in a broad array of clinical applications but have underperformed based on results from pre-clinical studies due to gaps in translating pre-clinical findings to human patients. Herein, we isolated mouse MSCs from pelvic bone marrow (BM^P), a preferred source for human MSCs, and compared their growth, differentiation, and immuno-modulatory activity to those derived from long bone marrow (BM^L), the traditional source of mouse MSCs. We report that BM^P-MSCs exhibit significantly enhanced growth kinetics in 5% and 21% oxygen saturation and superior bi-lineage differentiation and hematopoiesis-supporting activity as compared to BM^L-MSCs. Additionally, we show that TNF upregulates inducible nitric oxide synthase (NOS2) in BM^L- and BM^P- MSCs and augments their immune suppressive activity in cell-based assays, while interferon-gamma (INFG) upregulates indoleamine, 2-3, dioxygenase (IDO1) and enhances the immune suppressive activity of only BM^P-MSCs. These results indicate that mouse MSCs sourced from different bone compartments exhibit measurable differences in critical quality attributes, and these differences are comparable to those observed across species. Based on these differences, BM^P- MSCs represent a useful resource to model the behavior of human BM-derived MSCs.