Abstract:

This study constructed a comBO organoid system, establishing an integrated platform based on induced pluripotent stem cells, capable of simultaneously generating osteocytes, blood vessels, lymphatics, and bone marrow compartments. By optimizing the microenvironment with specific scaffolds, the system achieves stable expansion and can maintain lympho-myeloid hematopoietic potential over the long term. It can also create chimeric models to simulate physiological and pathological bone marrow microenvironments, clarify disease-related key signals, and provide a high-fidelity in vitro model for basic research on the bone-bone marrow microenvironment.

Results

Successfully constructed comBO organoids integrating osteocytes, blood vessels, lymphatics, and bone marrow compartments. The system demonstrates good scalability and reproducibility, and can maintain lympho-myeloid hematopoietic potential over the long term. The chimeric organoids can accurately model the bone-bone marrow microenvironment under both physiological and pathological conditions. In disease models, the remodeling process of the bone-bone marrow microenvironment was reproduced, and macrophage inhibitory factor signaling was identified as a key driving factor. Inhibiting this signaling can alleviate microenvironmental inflammation and regulate pathological cell proliferation.

Extension of Ideas

Relying on comBO organoids to deeply explore the interaction mechanisms between bone tissue and bone marrow hematopoietic and immune components; expanding this system to model bone-marrow microenvironments associated with various hematopoietic abnormalities; mining the core molecular mechanisms by which the bone-marrow microenvironment regulates the hematopoietic process based on the model.

Original Source

1. Journal: Cell Stem Cell
2. Publication Date: 2026-02-23
3. DOI: 10.1016/j.stem.2026.01.010
4. Authors: Yuqi Shen, Camelia Benlabiod, and several other researchers