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Modeling human bone marrow endosteal niches using induced pluripotent stem cells in xeno-free conditions

ABSTRACT: Endosteal bone marrow (BM) niches are crucial to sustain non-steady-state hematopoiesis but are challenging to be modelled in their cellular and molecular complexity in standardized, human settings. We report a developmentally-guided approach to generate a macro-scale organotypic model of BM endosteal niches (engineered vascularized osteoblastic niche, eVON) based on human induced pluripotent stem cells (hiPSC) and porous hydroxyapatite scaffolds. Vascular and osteoblastic cells derived from the same hiPSC self-assembled into complex and long-lasting vascular networks integrated within osteogenic matrix. The system supported hematopoiesis in vitro and was stable upon implantation in vivo. Transcriptomic analysis revealed osteogenic, vascular and neural cells expressing key niche signals (e.g., CXCL12, KITLG and VEGFA) in human-specific patterns. The eVON could be perturbed at cellular (removing vascular cells) and molecular (deregulating VEGF signaling) levels to study contribution of the endosteal vasculature to myelopoiesis. The eVON offers unprecedented possibilities to dissect human pathophysiological hematopoiesis in endosteal BM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE285292 | GEO | 2025/11/18

REPOSITORIES: GEO

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