A multi-niche microvascularized human bone marrow (hBM) on-a-chip elucidates key roles of the endosteal niche in hBM physiology

The human bone marrow (hBM) is a complex organ critical for hematopoietic and immune homeostasis, where many cancers metastasize. Understanding the fundamental biology of hBM in health diseases remain difficult due to complexity studying or manipulating BM humans. Accurate biomaterial-based vitro models microenvironment are further our understanding BM-niche advancing new clinical interventions. Here we report unique, 96-well format, microfluidic hBM-on-a-chip that incorporates endosteal, central marrow, perivascular niches BM. Osteogenic differentiation donor mesenchymal stromal cells (MSCs) produced robust mineralization on bottom surface (“bone-like endosteal layer”) device, subsequent seeding endothelial MSCs fibrin-collagen hydrogel network (“central marrow”) top created an interconnected 3D microvascular (“perivascular niche”). format allows eight independent “chips” be studied one plate, thereby increasing throughput reproducibility. We show this complex, multi-niche microtissue accurately mimics composition microphysiology, while providing key insights progenitor dynamics. Presence niche decreased proliferation increased maintenance CD34+ stem (HSCs). Upon exposure radiation, HSCs hBM-chips containing were less frequently apoptotic, suggesting potentially radio-protective role osteoblast surface. Our methods results provide broad platform creating multi-niche, high-throughput microphysiological (MPS) systems. Specifically, opens opportunities research therapeutics development, can used better understand normal impaired hematopoiesis, various pathologies, including cancer failures.