Abstract
Background: Clinical use of stromal stem cells in regenerative medicine is increasingly recognized as a promising treatment modality for age-related degenerative diseases based on the promising initial results of clinical trials. However, the magnitude of positive effects observed in these trials has been variable which can be explained by the lack of standardization of the stem cell products “cell product.” Bone marrow-derived stromal (also known mesenchymal) stem cells (BM-hMSC) and adipose tissue-hMSC (AD-hMSC) have been used interchangeably in clinical trials employing stromal stem cells as they were thought to be functionally identical. Methods: In the present study, we performed an extensive side-by-side comparison of BM-hMSC and AD-hMSC for their CD marker expression using FACS analysis, molecular phenotype using global mRNA gene expression analysis, and functional studies for their in vitro differentiation capacity to osteoblasts and adipocytes. Results: We observed both stromal cell populations were CD44+ CD13+ CD90+ CD29+ CD105+ CD14− HLDR−. We also observed that they express common genetic signature consisting of 13,667 genes with enrichment in a number of pathways relevant to stem cell biology, for example, focal adhesion, insulin signaling, and mitogen-activated protein kinase signaling. On the other hand, we observed significant differences in their molecular phenotype with 3282 and 1409 genes differentially expression in BM-hMSC and AD-hMSC, respectively. Further analysis revealed higher expression of genes associated with osteoblast differentiation in BM-hMSC and those of adipocyte differentiation in AD-hMSC which correlated with their differential capacity for osteoblast versus adipocyte differentiation, respectively. Conclusion: Our data suggest that the clinical use of MSC in therapy depend on MSC site of origin, and thus, BM-hMSC are better suited for clinical trials aiming at enhancing bone regeneration. We suggest that molecular phenotype of stem cells is relevant approach for stem cell screening before their clinical transplantation.
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