The effect of immobilized platelet derived growth factor AA on neural stem/progenitor cell differentiation on cell-adhesive hydrogels

Abstract

Neural stem/progenitor cells (NSPCs) hold great promise in regenerative medicine; however, controlling their differentiation to a desired phenotype within a defined matrix is challenging. To guide the differentiation of NSPCs, we first created a cell-adhesive matrix of agarose modified with glycine-arginine-glycine-aspartic acid-serine (GRGDS) and then demonstrated the multipotentiality of NSPCs to differentiate to the three primary cell types of the central nervous system on this matrix: neurons, oligodendrocytes and astrocytes. We then examined whether immobilized platelet derived growth factor AA (PDGF-AA) would promote differentiation similarly to the same soluble factor and found similar percentages of NSPCs differentiated to oligodendrocytes as determined by immunohistochemistry (IHC) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Interestingly, the gene expression of the differentiated oligodendrocytes was similar for 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) but different for myelin oligodendrocyte glycoprotein (MOG) in the presence of soluble PDGF-AA vs. immobilized PDGF-AA. These results demonstrate for the first time, that it is possible to control the differentiation of NSPCs, and specifically to oligodendrocytes, in cell-adhesive matrices with immobilized PDGF-AA.