To control the differentiation of neural progenitor cells (NPCs), the synergistic influence of topography, extracellular matrix (ECM) proteins, and soluble factors were investigated. Previously, in our laboratory, astrocyte-derived soluble factors were found to promote differentiation of adult hippocampal progenitor cells (AHPCs) into neurons when grown on a laminin substrate (Oh et al., J Biomed Mater Res A 2009;91:575-585). Here, we determined that the ECM protein on which AHPCs are cultured does not seem to alter this neurogenic effect or the differentiation of AHPCs when grown alone. However, AHPCs cultured on ECL (a combination of entactin, collagen, and laminin) in the presence of soluble factors from hippocampal astrocytes, differentiated into a significantly greater percentage of oligodendrocytes (approximately 34% on ECL vs. approximately 19% on laminin). Furthermore, a concomitant decrease in the percentage of proliferating cells was observed on the ECL (approximately 38% on ECL vs. approximately 55% on laminin). In addition, the increase in AHPC differentiation into oligodendrocytes on ECL occurred only in the presence of soluble factors from astrocytes, and not when AHPCs were cultured alone. Finally, we demonstrated that micro-scale topography did not influence the phenotypic differentiation in all conditions tested. These results show that a combination of astrocyte-derived soluble factors and ECM can dramatically affect the differentiation and proliferation of NPCs.
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