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An Organoid for Woven Bone |
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| Authors: | Anat Akiva Johanna Melke Sana Ansari Nalan Liv Robin van der Meijden Merijn van Erp Feihu Zhao Merula Stout Wouter H. Nijhuis Cilia de Heus Claudia Muñiz Ortera Job Fermie Judith Klumperman Keita Ito Nico Sommerdijk Sandra Hofmann |
| Affiliation: | 1. Department of Cell Biology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein, Nijmegen, Gelderland, 6525 The Netherlands;2. Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, North Brabant, 5600 The Netherlands Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, North Brabant, 5600 The Netherlands;3. Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, North Brabant, 5600 The Netherlands Laboratory of Materials and Interface Chemistry, Department of Chemical Engineering and Chemistry, Eindhoven, North Brabant, 5600 The Netherlands Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, North Brabant, 5600 The Netherlands;4. Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, Utrecht, 3584 The Netherlands;5. Laboratory of Materials and Interface Chemistry, Department of Chemical Engineering and Chemistry, Eindhoven, North Brabant, 5600 The Netherlands Department of Biochemistry, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein, Nijmegen, Gelderland, 6525 The Netherlands;6. Department of Cell Biology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein, Nijmegen, Gelderland, 6525 The Netherlands Electron Microscopy Center, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein, Nijmegen, Gelderland, 6525 The Netherlands;7. Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, North Brabant, 5600 The Netherlands Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, North Brabant, 5600 The Netherlands Zienkiewicz Centre for Computational Engineering, College of Engineering, Swansea University, Swansea, SA1 8EN UK;8. Laboratory of Materials and Interface Chemistry, Department of Chemical Engineering and Chemistry, Eindhoven, North Brabant, 5600 The Netherlands;9. Department of Orthopaedic Surgery, University Medical Centre Utrecht, Wilhelmina Children's Hospital, Utrecht, Utrecht, 3584 The Netherlands;10. Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, North Brabant, 5600 The Netherlands |
| Abstract: | 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). |
| Keywords: | 3D cell culture 3D electron microscopy biomineralization bone model organoid |