We have created a novel class of collagen-based biomaterials that mimics patterned heterogeneities found in the native BM while also enabling in situ analysis of the HSCs. Gradient generation with different materials (cells/beads) using different collagen densities and their subsequent analysis demonstrates the versatility of this biomaterial system. This project will develop transformative new tools to systematically explore the significance of cell-based cues on HSC fate and provide significant new insight into the relationship between extrinsic cues and the internal signaling cascades regulating HSC biology. Improved understanding of HSC fate decision is critical for optimizing biomaterial systems for ex vivo expansion of clinically relevant hematopoietic cells and for studying the etiology, niche regulation and treatment of hematopoietic pathologies.
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