An Organoid for Woven Bone
An Organoid for Woven Bone
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DOI：
10.1002/adfm.202010524
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发表时间：
2021-03-09
影响因子：
19
通讯作者：
Hofmann, Sandra
中科院分区：
文献类型：
--
作者：
Akiva, Anat;Melke, Johanna;Hofmann, Sandra
骨形成（骨生成）是一个复杂的过程，其中细胞分化和矿化有机基质的产生是同步的，以产生混合的层次结构。为了研究健康和疾病中的成骨机制，非常需要并行捕获细胞和基质形成过程的功能模型系统。基于干细胞的类器官很有希望作为功能性、自组织的3D体外模型，用于研究各种组织的生理和病理。然而，对于人骨，还没有这样的功能模型系统。本研究报告了人骨髓基质细胞在体外分化为成骨细胞和骨细胞的功能性3D自组织共培养物，为早期骨（编织骨）形成创造了类器官。它证明了类器官的形成，其中骨细胞包埋在由成骨细胞产生并在生物控制下矿化的胶原基质中。与体内骨细胞一样，包埋的骨细胞通过表达硬化蛋白显示网络形成和通讯。目前的系统形成了最完整的3D活体体外模型系统，用于研究生理和病理情况下以及外部触发因素（机械刺激，药物给药）影响下的骨生成。
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).