Chen Amanda X, Chhabra Arnav, Song H-H Greco, Fleming Heather E, Chen Christopher S, Bhatia Sangeeta N
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Adv Funct Mater. 2020 Nov 25;30(48). doi: 10.1002/adfm.201910442. Epub 2020 Jun 8.
Engineered tissue models comprise a variety of multiplexed ensembles in which combinations of epithelial, stromal, and immune cells give rise to physiologic function. Engineering spatiotemporal control of cell-cell and cell-matrix interactions within these 3D multicellular tissues would represent a significant advance for tissue engineering. In this work, a new method, entitled CAMEO (Controlled Apoptosis in Multicellular tissues for Engineered Organogenesis) enables the non-invasive triggering of controlled apoptosis to eliminate genetically-engineered cells from a pre-established culture. Using this approach, the contribution of stromal cells to the phenotypic stability of primary human hepatocytes is examined. 3D hepatic microtissues, in which fibroblasts can enhance phenotypic stability and accelerate aggregation into spheroids, were found to rely only transiently on fibroblast interaction to support multiple axes of liver function, such as protein secretion and drug detoxification. Due to its modularity, CAMEO has the promise to be readily extendable to other applications that are tied to the complexity of 3D tissue biology, from understanding organoid models to building artificial tissue grafts.
工程组织模型包含多种复合组件，其中上皮细胞、基质细胞和免疫细胞的组合产生生理功能。对这些三维多细胞组织内细胞间和细胞与基质相互作用进行时空工程控制，将是组织工程的一项重大进展。在这项工作中，一种名为CAMEO（用于工程化器官发生的多细胞组织中的可控凋亡）的新方法能够非侵入性地触发可控凋亡，以从预先建立的培养物中消除基因工程细胞。利用这种方法，研究了基质细胞对原代人肝细胞表型稳定性的贡献。结果发现，三维肝微组织中，成纤维细胞可增强表型稳定性并加速聚集成球体，该组织仅短暂依赖成纤维细胞相互作用来支持肝功能的多个方面，如蛋白质分泌和药物解毒。由于其模块化特性，CAMEO有望很容易扩展到其他与三维组织生物学复杂性相关的应用中，从理解类器官模型到构建人工组织移植物。
