Bone formation (osteogenesis) is a complex process in which cellular differentiation and the generation of a mineralized organic matrix are synchronized to produce a hybrid hierarchical architecture. To study the mechanisms of osteogenesis in health and disease, there is a great need for functional model systems that capture in parallel, both cellular and matrix formation processes. Stem cell‐based organoids are promising as functional, self‐organizing 3D in vitro models for studying the physiology and pathology of various tissues. However, for human bone, no such functional model system is yet available. This study reports 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. It demonstrates the formation of an organoid where osteocytes are embedded within the collagen matrix that is produced by the osteoblasts and mineralized under biological control. Alike in in vivo osteocytes, the embedded osteocytes show network formation and communication via expression of sclerostin. The current system forms the most complete 3D living in vitro model system to investigate osteogenesis, both in physiological and pathological situations, as well as under the influence of external triggers (mechanical stimulation, drug administration).
Cell migration research has become a high-content field. However, the quantitative information encapsulated in these complex and high-dimensional datasets is not fully exploited owing to the diversity of experimental protocols and non-standardized output formats. In addition, typically the datasets are not open for reuse. Making the data open and Findable, Accessible, Interoperable, and Reusable (FAIR) will enable meta-analysis, data integration, and data mining. Standardized data formats and controlled vocabularies are essential for building a suitable infrastructure for that purpose but are not available in the cell migration domain. We here present standardization efforts by the Cell Migration Standardisation Organisation (CMSO), an open community-driven organization to facilitate the development of standards for cell migration data. This work will foster the development of improved algorithms and tools and enable secondary analysis of public datasets, ultimately unlocking new knowledge of the complex biological process of cell migration.
25 26 ^equal contribution 27 Corresponding authors: anat.akiva@radboudumc.nl ; nico.sommerdijk@radboudumc.nl; 28 s.hofmann@tue.nl 29 Stem cell-based organoids are promising as functional, self-organizing 3D in vitro models for 30 studying the physiology and pathology of various tissues 1 . Bone formation (osteogenesis) is a 31 complex process in which i) cellular differentiation and ii) the generation of a mineralized organic 32 matrix are synchronized to produce a hybrid hierarchical architecture. To study the molecular 33 mechanisms of osteogenesis in health and disease there is great need for organoids that capture 34 both processes in parallel 2 , however, for human bone no such functional model system is yet 35 available 3 . 36 Here, we report the in vitro differentiation of human bone marrow stromal cells into a functional 37 3D self-organizing co-culture of osteoblasts and osteocytes, creating an organoid for early stage 38 bone (woven bone) formation. We demonstrate that the osteocytes form a network showing cell-39 cell communication via the expression of sclerostin, embedded within the collagen matrix that is 40 formed by the osteoblasts and mineralized under biological control. 41
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.