Journal article
comBO: A combined human bone and lympho-myeloid bone marrow organoid for preclinical modeling of hematopoietic disorders
- Abstract:
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 21.4MB, Terms of use)
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(Preview, Supplementary materials, pdf, 91.6MB, Terms of use)
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- Publisher copy:
- 10.1016/j.stem.2026.01.010
Authors
+ Wellcome Trust
More from this funder
- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 323265/Z/24/Z
- 218649/Z/19/Z
- 216632/Z/19/Z
+ Cancer Research UK
More from this funder
- Funder identifier:
- https://ror.org/054225q67
- Grant:
- RCCCSF-Nov21\100004
+ Medical Research Council
More from this funder
- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MC_UU_00029/7
- MR/X012743/1
- MC_UU_12025
- G0902418
+ UK Research and Innovation Medical Research Council
More from this funder
- Funder identifier:
- 10.13039/501100000265
- Grant:
- MC_UU_00029/7
- Publisher:
- Elsevier
- Journal:
- Cell Stem Cell More from this journal
- Volume:
- 33
- Issue:
- 3
- Pages:
- 421-437
- Place of publication:
- United States
- Publication date:
- 2026-02-23
- Acceptance date:
- 2026-01-21
- DOI:
- EISSN:
-
1875-9777
- ISSN:
-
1934-5909
- Pmid:
-
41734765
- Language:
-
English
- Pubs id:
-
2382599
- Local pid:
-
pubs:2382599
- Source identifiers:
-
W7131088910
- Deposit date:
-
2026-04-28
- ARK identifier:
Terms of use
- Copyright holder:
- Shen et al.
- Copyright date:
- 2026
- Rights statement:
- ©2026 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Licence:
- CC Attribution (CC BY)
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