Adult human mesenchymal stem cells (hMSCs) harvested from various tissues similarly exhibit multipotential characteristics. However, it is unclear if hMSCs from different tissue origins undergo an identical differentiation process. Objectives: To develop an understanding of the gene regulatory events leading from an undifferentiated adult hMSC derived from bone marrow and adipose tissue to a mature osteoblast. Methods: hMSCs harvested from adipose tissue (AD-hMSCs) and bone marrow (BM-hMSCs) were subjected to osteogenic differentiation. The transcriptome profiles of uninduced and osteogenically-induced BM-hMSC and AD-hMSCs were examined using a custom-made cDNA microarray containing 55 extracellular matrix related genes (ECMGs) and 96 human commonly expressed housekeeping genes (HKGs). BM-hMSC viability during osteogenic differentiation was evaluated using live/dead Viability/Cytotoxity kit to determine whether the culture system utilizes a selection and elimination process in which unfit cells undergo apoptosis. Results: Undifferentiated AD-hMSCs and BM-hMSCs actively expressed ECMGs, and during the course of osteogenic differentiation, 19 and 27 ECMGs underwent considerable down-regulation, respectively. The rest of genes were maintained at the similar expression level of the corresponding uninduced hMSCs. During this time period, cell viability was well sustained suggesting that the observed down-regulation did not occur by selection and elimination of unfit cells from the whole hMSC population. Furthermore, the down-regulated genes in BM-hMSCs and AD-hMSCs were not identical. Fibronectin, fibroblast growth factor receptor 4 and collagen 9A1 genes underwent down-regulation in osteogenic BM-hMSCs; but these genes were not modulated in osteogenic AD-hMSCs. On the contrary, osteopontin, collagen 5A2 and collagen 15A1 genes were down-regulated only in osteogenic AD-hMSCs. Conclusions: These data indicate that guided differentiation of hMSCs may employ, in part, a silencing mechanism of discordant genes that are sensitive to phenotype development, and the postulated gene silencing may compensate the constitutive variation between hMSCs derived from heterogenic tissue sources.

Back to the Mineralized Tissue Program
Back to the IADR/AADR/CADR 85th General Session and Exhibition (March 21-24, 2007)

Top Level Search