Title of Abstract
While neural progenitor cells (NPCs) and their progeny have significant therapeutic promise, the difficulty and cost of expanding and delivering a large number of NPCs remain significant barriers to widespread clinical use. Recently, 3D hydrogels have been proposed as in vitro culture platforms for the expansion of stem cell populations to overcome the space limitations of 2D culture. However, very little is known about which 3D material properties are required to maintain NPCs in an undifferentiated state for expansion. Using a family of protein-engineered biomaterials, we demonstrate that 3D matrix stiffness does not correlate with the maintenance of NPC stemness over a broad range of matrix mechanical properties (E~0.5-50 kPa). In contrast, matrix degradability strongly correlated with the expression of NPC stem markers and NPC proliferation in three different biomaterial systems. Our results have identified matrix remodeling as a previously unknown requirement for maintenance of NPC stemness in 3D hydrogels and suggest that adaptable biomaterials will be useful for expansion and transplantation of therapeutically relevant numbers of NPCs.
Heilshorn's interests include biomaterials in regenerative medicine, engineered proteins with novel assembly properties, microfluidics and photolithography of proteins, and synthesis of materials to influence stem cell differentiation. Current projects include tissue engineering for spinal cord and blood vessel regeneration, designing injectable materials for use in stem cell therapies, and the design of microfluidic devices to study the directed migration of cells (i.e., chemotaxis).