comBO: A combined human bone and lympho-myeloid bone marrow organoid for pre-clinical modelling of haematopoietic disorders

作者：Yuqi Shen, Camélia Benlabiod, Antonio Rodriguez-Romera, Edmund Watson, Jasmeet S. Reyat, Kristian Gurashi, Shady Adnan Awad, Rupen Hargreaves, Samuel Kemble, Charlotte G. Smith, Adam P. Croft, Udo Oppermann, Natalie J. Jooss, Zoë C. Wong, Julie Rayes, Adam J. Mead, Anindita Roy, Sarah Gooding, Bethan Psaila, Abdullah O. Khan · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.1101/2025.02.16.638505 · 被引用次数：3 · 研究领域：Hematological disorders and diagnostics、Hematopoietic Stem Cell Transplantation、Myeloproliferative Neoplasms: Diagnosis and Treatment

Abstract The bone marrow supports lifelong blood and immune cell production. Current human bone marrow organoid models do not include both lymphoid and myeloid elements and lack the complexity of stromal cell types present in native haematopoietic tissues, precluding the accurate ex vivo modelling of human pathologies. Here we introduce “comBOs” ( com bined b one and lympho-myeloid bone marrow o rganoids) that include osteolineage, vascular, lymphoid and myeloid cells. comBOs are generated by the differentiation of induced pluripotent stem cells guided by physiologically-relevant oxygen and cytokine exposures within an innovative granular microgel scaffold to increase scalability and reproducibility. We demonstrate that comBOs can be used to generate “chimeroids” - incorporating healthy or aberrant cells from adult donors – and recapitulate features of diseased microenvironments. ComBOs are one of the most physiologically-relevant human organoid systems to date, and this study showcases the potential of 3D in vitro disease models for discovery science and translational studies.