comBO: A combined human bone and lympho-myeloid bone marrow organoid for preclinical modeling of hematopoietic disorders
The bone marrow is the primary site of blood and immune cell production in postnatal life. Current human models do not capture lympho-myeloid hematopoiesis and the stromal diversity needed for lifelong blood and immune maintenance. Here, we introduce comBO (combined bone and lympho-myeloid bone marrow organoid), a scalable induced pluripotent stem cell (iPSC)-derived system that generates osteolineage, vascular, lymphoid, and myeloid compartments within a single organoid. Developed under physioxia in granular microgel scaffolds, comBOs improve scalability and reproducibility and sustain long-term lympho-myeloid potential in serial organoid re-seeding assays. Incorporating healthy or malignant donor cells produces "chimeroids" that model physiological and pathological states. Using multiple myeloma as an exemplar, comBOs recapitulate niche remodeling and identify macrophage inhibitory factor (MIF) signaling as a disease driver. MIF inhibition reduces inflammation and myeloma proliferation, highlighting its therapeutic potential. comBOs offer a physiologically faithful bone marrow platform for disease modeling and therapeutic discovery in translational hematology and immunology.
Authors
- Camélia Benlabiod (ORCID: https://orcid.org/0000-0001-7119-9326)
- Samuel Kemble (ORCID: https://orcid.org/0000-0002-3359-7718)
- Adam Mead
- Sarah Gooding (ORCID: https://orcid.org/0000-0002-1549-7043)
- Zoë C. Wong (ORCID: https://orcid.org/0000-0001-6006-1233)
- Natalie J. Jooss (ORCID: https://orcid.org/0000-0002-2314-4993)
- Jasmeet S. Reyat (ORCID: https://orcid.org/0000-0003-3247-9186)
- Kristian Gurashi (ORCID: https://orcid.org/0000-0002-5540-3398)
- Alex Fower
- Rupen Hargreaves
- Lauren C. Murphy (ORCID: https://orcid.org/0000-0001-9506-2762)
- Julie Rayes (ORCID: https://orcid.org/0000-0003-0499-6880)
- Antonio Rodriguez-Romera (ORCID: https://orcid.org/0000-0001-7193-9144)
- Shady Adnan Awad (ORCID: https://orcid.org/0000-0001-6205-7799)
- Yuqi Shen (ORCID: https://orcid.org/0009-0008-9114-8743)
- Charlotte G. Smith
- Bethan Psaila
- Amirpasha Moetazedian
- Eleanor Murphy
- Abdullah O. Khan
- Udo Oppermann
- Edmund Watson
- Adam P. Croft
- Anindita Roy
- Alia Welsh
Institutions
- University of Hull (GB)
- John Radcliffe Hospital (GB)
- NIHR Birmingham Liver Biomedical Research Unit (GB)
- MRC Weatherall Institute of Molecular Medicine (GB)
- MRC Human Immunology Unit (GB)
- Oxford BioMedica (United Kingdom) (GB)
- NIHR Birmingham Biomedical Research Centre (GB)
- University of Birmingham (GB)
Publication Details
- Journal
- Cell stem cell
- Published
- 2026-02-23
- DOI
- https://doi.org/10.1016/j.stem.2026.01.010
- Citations
- 2
- Primary Topic
- Hematopoietic Stem Cell Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 70.83