THE EFFECTS OF SCAFFOLD MORPHOLOGY ON GENE EXPRESSION PROFILES OF PRIMARY HUMAN BONE MARROW STROMAL CELLS AS REVEALED BY MICROARRAYS
Bryan A. Baker, Girish Kumar, Kaushik Chatterjee, Jennifer H. McDaniel, P. Scott Pine, Mark L. Salit, and Carl G. Simon Jr.
The ability to cue cellular response based on scaffold properties has been well established in the field of tissue engineering. Particularly, scaffold morphology has been shown to promote differentiation in adult stem cells. However, the mechanisms by which scaffold morphology directs cellular processes such as differentiation is not fully understood. The present work examines the influence of scaffold morphology on osteogenesis and gene expression of primary human bone marrow stromal cells, adult stem cells isolated from bone marrow with the capacity to undergo differentiation into osteogenic, chondrogenic, or adipogenic lineages. Cells were cultured on both 3D nanofibers and 2D film scaffolds and mRNA expression was analyzed by cDNA microarray. A classification strategy was developed based on the phenotypic expression of an independently verifiable marker to facilitate comparison of mRNA expression profiles. Genes determined to be differentially expressed between independently verified classes were correlated with gene ontology analysis to elucidate biological processes influenced by scaffold morphology. Our results indicate that the 3D nanofiber scaffolds may mimic the effect of soluble osteogenic supplements in promoting osteogenesis via the TGF-β signaling pathway, whereas 2D films do not. These results contribute to the development of measurement tools to aid our understanding of the effects scaffold properties have on stem cell differentiation.