Elucidating Cell Fate Regulation of the Bone Marrow Vascular Niche Through Development of Engineered Extracellular Matrices

Haematopoietic stem and progenitor cells (HSPCs) are crucial to the curative treatment of a variety of leukaemias and autoimmune diseases. However, their rapid differentiation and exhaustion within 72 hours ex vivo poses a barrier to efficient treatment. Here, we have developed a culture method that mimics that of the in vivo haematopoietic vascular niche in order to extend viability and maintain multipotency of HSPCs. The two-factor approach combined the paracrine support of endothelial cells as well as the structural and chemical support of an engineered two-dimensional scaffold comprised of several extracellular matrix (ECM) components. HSPCs that were co-cultured on ECM-mimicking scaffolds maintained higher viability in culture for up to seven days in comparison to solo-culture counterparts, and functional tests revealed an improvement in colony formation potential. Continued development of the culture system and understanding of the molecular pathways at play can lead to improved patient outcomes after transplantation.