Controlled Apoptosis of Stromal Cells to Engineer Human Microlivers. (8th June 2020) - Chen, Amanda X.
Abstract: Engineered tissue models comprise a variety of multiplexed ensembles in which combinations of epithelial, stromal, and immune cells give rise to physiologic functions. 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 (C ontrolled A poptosis in M ulticellular tissues for E ngineered O rganogenesis) enables the noninvasive 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, are 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 in vitro organoid models to building artificial tissue grafts. Abstract : Like their native counterparts, bioengineered tissues often consist of multiple cell lineages to recapitulate complex physiology. Current tools are limited in resolving the dynamic contributions of multicellular interactions. Here, CAMEO (Controlled Apoptosis in Multicellular Tissues for Engineered Organogenesis) is presented as a new strategy to precisely manipulate tissue composition, which enables new insight into the complexity of 3D tissue biology.