Human iPSC-derived bone marrow organoids with integrated hematopoietic and T cell-supportive niches
The anatomical separation of bone marrow and thymus restricts the efficient generation of human immune cells in vitro, limiting experimental platforms for integrated hematopoiesis. This study engineered human induced pluripotent stem cell-derived bone marrow organoids (iBMOs) that self-organize into stromal, vascular, and hematopoietic compartments and provide microenvironmental cues supportive of T cell differentiation. iBMOs produced hematopoietic progenitors and yielded stable stromal stem cell lines (iBOSS) expressing Notch-associated molecules, which supported differentiation of iPSC-derived hematopoietic progenitors toward T-lineage and dendritic cell-associated populations in vitro. Following transplantation into immunodeficient mice, iBMOs sustained human erythropoiesis and underwent bone formation, demonstrating autonomous niche activity in vivo. The iBMO–iBOSS platform functionally integrates essential features of bone marrow and T cell–supportive stromal niches, enabling coordinated generation of multiple hematopoietic lineages from human iPSCs. This system offers a reproducible and scalable source of immune cells for translational immunotherapy and expands understanding of human hematopoietic biology, opening avenues for engineering synthetic, patient-specific immune systems.