An Organoid for Woven Bone

Stem cell-based organoids are promising as functional, self-organizing 3D in vitro models for studying the physiology and pathology of various tissues1. Bone formation (osteogenesis) is a complex process in which i) cellular differentiation and ii) the generation of a mineralized organic matrix are synchronized to produce a hybrid hierarchical architecture. To study the molecular mechanisms of osteogenesis in health and disease there is great need for organoids that capture both processes in parallel2, however, for human bone no such functional model system is yet available3. Here, we report the in vitro differentiation of human bone marrow stromal cells into a functional 3D self-organizing co-culture of osteoblasts and osteocytes, creating an organoid for early stage bone (woven bone) formation. We demonstrate that the osteocytes form a network showing cell-cell communication via the expression of sclerostin, embedded within the collagen matrix that is formed by the osteoblasts and mineralized under biological control.