Osteoblast/fibroblast coculture derived bioactive ECM with unique matrisome profile facilitates bone regeneration
Osteoblast/fibroblast coculture derived bioactive ECM with unique matrisome profile facilitates bone regeneration
复制标题
成骨细胞/成纤维细胞共培养衍生的生物活性 ECM 具有独特的基质体特征，可促进骨再生
DOI：
10.1016/j.bioactmat.2020.06.017
复制
发表时间：
2020-12-01
影响因子：
18.9
通讯作者：
Zhao, Jiyuan
中科院分区：
文献类型：
--
作者：
Li, Mei;Zhang, Anqi;Zhao, Jiyuan
细胞外基质（Extracellular matrix，ECM）具有模拟组织龛的功能，通过募集内源性细胞和刺激自愈合过程，促进组织原位再生。然而，如何在体外构建具有独特基质体的复杂组织特异性细胞外基质，是细胞外基质基生物材料在组织工程和再生医学中的一个挑战。在此，我们引入共培养系统，以细胞间通讯为指导构建骨模拟ECM小生境。在共培养中，成纤维细胞通过细胞外囊泡促进成骨细胞的成骨分化。所产生的ECM（MN-ECM）显示出独特的外观形态和生物成分。MN-ECM在体外可促进细胞增殖、粘附和成骨矿化，在体内可促进骨再生。此外，蛋白质组学分析用于阐明MN-ECM的分子机制，其揭示了特定的基质体签名。本研究为在共培养体系中通过细胞间通讯产生具有组织模拟小生境的ECM提供了一种新的策略，沿着对骨组织工程中细胞调控ECM小生境的深入理解，推动了组织生物活性ECM工程的发展。
Extracellular matrix (ECM) with mimetic tissue niches was attractive to facilitate tissue regeneration in situ via recruitment of endogenous cells and stimulation of self-healing process. However, how to engineer the complicate tissue specific ECM with unique matrisome in vitro was a challenge of ECM-based biomaterials in tissue engineering and regenerative medicine. Here, we introduced coculture system to engineer bone mimetic ECM niche guided by cell-cell communication. In the cocultures, fibroblasts promoted osteogenic differentiation of osteoblasts via extracellular vesicles. The generated ECM (MN-ECM) displayed a unique appearance of morphology and biological components. The advantages of MN-ECM were demonstrated with promotion of multiple cellular behaviors (proliferation, adhesion and osteogenic mineralization) in vitro and bone regeneration in vivo. Moreover, proteomic analysis was used to clarify the molecular mechanism of MN-ECM, which revealed a specific matrisome signature. The present study provides a novel strategy to generate ECM with tissue mimetic niches via cell-cell communication in a coculture system, which forwards the development of tissue-bioactive ECM engineering along with deepening the understanding of ECM niches regulated by cells for bone tissue engineering.