Transcriptome profiling of mesenchymal stem cells cultured in 3D functionalized hydrogels

Therapeutic applications for mesenchymal stem/stromal cells (MSCs) are growing, including the treatment of chronic wounds ; however, the successful implementation of these therapies requires the development of appropriate MSC delivery systems. Hydrogels are ideally suited to cultivate MSCs in 3D but tuning their properties to match their specific in vivo applications remains a challenge. Herein, we have tethered integrin-binding small molecules to well-defined, cell-degradable hydrogels based on bioinert poly(ethylene glycol) (PEG) tethered with specific integrin-binding peptides and have characterized the resulting effects that these culture systems have on the MSC transcriptome when compared to 2D cultured and untethered 3D hydrogel cultured MSCs. The 3D culture systems resulted in the differential expression of 1,911 genes, many of which were related to the production of extracellular matrix proteins and/or MSC differentiation. In general, genes important for osteogenic differentiation were upregulated in 3D hydrogel cultures; however, the expression of these genes could be partially suppressed by tethering an integrin-binding RGD peptide within the hydrogel.