Transplantation of stem cells is a promising potential therapy for central nervous system disease and injury. The capacity for self-renewal, proliferation of progenitor cells, and multi-lineage potential underscores the need for controlling stem cell fate. Furthermore, transplantation within a hostile environment can lead to significant cell death and limited therapeutic potential. Tissue-engineered materials have been developed to both regulate stem cell fate, increase transplanted cell viability, and improve therapeutic outcomes. Traditionally, regulation of stem cell differentiation has been driven through soluble signals, such as growth factors. While these signals are important, insoluble factors from the local microenvironment or extracellular matrix (ECM) molecules also contribute to stem cell activity and fate. Understanding the microenvironment factors that influence stem cell fate, such as mechanical properties, topography, and presentation of specific ECM ligands, is necessary for designing improved biomaterials. Here we review some of the microenvironment factors that regulate stem cell fate and how they can be incorporated into biomaterials as part of potential CNS therapies.
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