The rise of bone marrow organoids as next-generation models for blood formation and failure

Bone marrow organoids (BMOs) are three-dimensional (3D) cell culture models that recapitulate key structural and functional features of the bone marrow (BM) niche. BMOs offer important advantages in hematopoietic research by modeling key aspects of human hematopoiesis compared with classical in vitro 2D and 3D cellular models including bioreactors, BM-on-a-chip platforms, 2D models or BM ossicles by better recreating the 3D architecture, cellular heterogeneity, and spatial organization of the BM microenvironment. They offer a scalable and cost-effective alternative to animal models and reduce the need for animal experiments. Induced pluripotent stem cell (iPSC)-derived BMOs can be generated from a patient's own cells, enabling personalized disease modeling and drug testing and are highly amenable to gene editing technologies allowing precise modifications to study gene function or model diseases. Recent landmark studies from Christoph Klein and Abdullah Khan have established protocols for the generation of BMOs and demonstrated their applications in disease modeling. Here, we reviewed the critical steps in BMO generation, their structural/functional validation, and discussed how BMOs can be applied to model inflammatory responses, rare genetic bone marrow failure syndromes, and multiple myeloma. These advancements demonstrate BMOs' growing potential as powerful tools in hematopoietic research and will pave the way for further innovation and increasingly refined systems in future studies.