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Shen et al. (2026)
Lead image shows a microscope image of a combined bone and bone marrow organoid that captures vessels and blood cells. These organoids have always reminded the research team of celestial bodies, so the image has been edited to resemble a galaxy.
Published in Cell Stem Cell, the study introduces comBO (combined Bone and bone marrow Organoid), a scalable and modular platform that recreates key structural and functional features of the human bone marrow. comBO enables long-term modelling of human blood and immune cell production and provides a new way to study diseases directly in a human tissue context.
Despite decades of investment, many therapies for blood cancers and immune disorders fail in late-stage clinical trials due to poor translation from preclinical models. Animal models and simplified lab-grown cell systems often fail to capture the full complexity of human bone marrow biology, limiting their ability to predict what will happen in patients.
comBo was developed to address this gap. It integrates bone-forming, supportive and blood-forming cells into a single engineered human microenvironment. Within this system, researchers were able to sustain long-term human blood cell production (haematopoiesis) and recreate the specialised niches in the bone marrow that regulate stem cell behaviour and immune cell production.
First author Dr Yuqi Shen, a postdoctoral researcher in the MRC Molecular Haematology Unit, said:
Many therapies fail not because the target is wrong, but because the model is. We wanted to build a system that more closely reflects the human bone marrow environment that diseases actually exploit.
In collaboration with Dr Sarah Gooding, the team at the MRC Weatherall Institute of Molecular Medicine used comBO to model multiple myeloma, a blood cancer that grows within the bone marrow and alters its surrounding environment. Myeloma cells do not grow and divide outside of the body, posing a major challenge for developing new treatments. When real cancer cells from patients were introduced into comBO, they survived, grew and reshaped the surrounding tissue, mirroring what happens in patients. These findings show that comBO can function as a human model platform for evaluating therapeutic efficacy and microenvironment-driven treatment resistance in a clinically relevant system before therapies enter trials.
Speaking about the implications of the study for translation research and therapy development, senior author Dr Abdullah Khan said:
By engineering a human system that captures the complexity of blood and immune cell production, we can model blood cancers and immune diseases in a way that is far more relevant to patients. This means we are moving to more predictive preclinical testing
comBO allows us to test therapies within realistic human microenvironments, investigate how the bone marrow niche drives treatment resistance, and reduce our reliance on animal models that often fail to predict what happens in the clinic.
As an engineered bone marrow, comBO can be integrated into multi-tissue, ‘body-on-a-chip’ models – acting as a source of blood and immune cells for other disease models. Capturing these interactions, which are complex and varied, has been a major challenge in building tractable human disease models. The team recently tested this approach by coupling comBO with a heart organoid in a modular platform that mimicked immune recruitment in heart injury. Immune cells are critical to repair and regeneration in the heart, but understanding how they contribute to these processes in the human context has proven difficult.
By providing a human platform that captures the complexity of bone marrow biology, comBO offers a new foundation for studying blood cancers, immune disorders and regenerative processes. This has the potential to reduce reliance on animal models and accelerate therapeutic discovery.
Read the full paper in Cell Stem Cell: comBO: A combined human bone and lympho-myeloid bone marrow organoid for preclinical modeling of hematopoietic disorders