Authors
Lee, J., Kawasaki, T., Tabata, L., Chen, J., Uchiyama, T., Yamazaki, S., Umezawa, A., Akutsu, H.
Abstract
Human bone marrow generates blood cells but critically lacks the thymic environment required for T cell development. Developing an integrated in vitro platform that reconstitutes both functions simultaneously remains a major challenge in regenerative and immune medicine. We asked whether a synthetic marrow could be engineered to provide both capacities. Using human induced pluripotent stem cells, we created self-organizing bone marrow organoids (iBMOs) that faithfully reproduced native stromal and vascular structures and, remarkably, supported robust thymus-like T cell differentiation. iBMOs directed hematopoietic progenitors toward functional T and dendritic cells. When engrafted into immunodeficient mice, they autonomously sustained human erythropoiesis and de novo bone formation in vivo. Single-cell transcriptomics revealed a complex niche architecture, including a hybrid cluster co-expressing stem, endothelial, and stromal markers, key to understanding this dual functionality. This bioengineered organoid-stromal system unifies bone marrow and thymic functions in a single human-derived platform, offering a scalable source of immune cells for adoptive cell therapies and regenerative applications, as well as a versatile model for studying human hematopoiesis and immunity.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 07 Nov 2025.
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