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This study explores how to construct a bone marrow organoid model that is closer to the physiological state of the human body. The research team from institutions such as the University of Oxford has developed an innovative system called comBO (a combined organoid of human bone and lymph-mesenchymal bone marrow). This system is based on induced pluripotent stem cells (iPSCs) and can simultaneously generate the bone compartment, blood vessels, lymph sinuses, and myeloid hematopoietic microenvironment in a single culture system, precisely simulating the complex cellular composition and spatial structure of real bone marrow. The related literature was published in the top journal of cell biology, "Cell Stem Cell".
Key innovations
01 Bionic structure design, integrating lymph-mesenchymal dual lineages
Unlike previous organoids that could only simulate a single hematopoietic lineage, comBO is the first to simultaneously cultivate lymphoid and myeloid bone marrow microenvironments in the same structure. It not only supports the generation of erythroid and myeloid cells, but also successfully maintains the development and maturation of lymphocytes, more comprehensively reproducing the core functions of the bone marrow as a lifelong hematopoietic and immune organ.
02 Engineered microenvironment, breaking through size and reproducibility bottlenecks
The research team used particle microgel scaffolds as a physical support matrix. This innovation not only solved the problem of easy necrosis in traditional organoids by improving the efficiency of oxygen and nutrient exchange, but also significantly improved the reproducibility and scalability of the experiments, laying a technical foundation for large-scale drug screening and mechanism research.
03 Dynamic disease modeling, revealing the mechanism of niche remodeling
By implanting healthy or malignant cells into comBO, a "chimeric" model that can truly reflect the pathological state was constructed. In the application of multiple myeloma, this model successfully captured the process of bone marrow niche remodeling induced by tumor cells and identified macrophage migration inhibitory factor (MIF) as a key driving molecule, providing a new perspective for understanding disease progression.
Journal name: Cell Stem Cell
Publication date: 2026-02-23
DOI: 10.1016/j.stem.2026.01.010 Research Team: Yuqi Shen, Camelia Benlabiod, Edmund Watson, and several other researchers including Abdullah O. Khan, among others. The collaborating institutions include the MRC Weatherall Institute of Molecular Medicine at the University of Oxford, and other organizations.
