Abstract
Mesenchymal stem cells (MSCs) have broad-based therapeutic potential in regenerative medicine. However, a major barrier to their clinical utility is that MSCs from different tissues are highly variable in their regenerative properties. In this study, we defined the molecular and phenotypic identities of different MSC populations from different osseous tissue sites of different patients and, additionally, determined their respective regenerative properties. MSCs from 6 patients were isolated from either bone marrow of the iliac crest (BMSCs) or alveolar bone tissue (aBMSCs), and flow cytometry revealed that regardless of the tissue source, MSC immunotypes had the same expression of MSC markers CD73, CD90, and CD105. However, transcriptomic analyses revealed 589 genes differentially expressed (DE) between BMSCs and aBMSCs, including eightfold higher levels of bone morphogenetic protein 4 (BMP-4) in aBMSCs. In striking contrast, gene expression of MSCs derived from the same tissue, but between different patients (i.e., BMSCs to BMSCs, aBMSCs to aBMSCs), showed only 38 DE BMSC genes and 51 DE aBMSC genes. A protein array showed that aBMSC and BMSC produced equivalent levels of angiogenic cytokines; however, when placed in angiogenesis model systems, aBMSCs induced significantly more capillaries in vitro and in vivo. Finally, cell transplantation of MSCS into osseous defects showed that the bone regenerative capacity of aBMSCs was significantly greater than that of BMSCs. This study is the first to link the molecular, phenotypic, and regenerative properties of different MSCs from different patients and provides novel insights toward MSC differences based on the osseous tissue origin.