Controlled Apoptosis of Stromal Cells to Engineer Human Microlivers

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...

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Bibliographic Details
Published in:Advanced functional materials 2020-11, Vol.30 (48), p.n/a
Main Authors: Chen, Amanda X., Chhabra, Arnav, Song, Hyun‐Ho Greco, Fleming, Heather E., Chen, Christopher S., Bhatia, Sangeeta N.
Format: Article
Language:English
Subjects:
Apoptosis
Artificial tissues
biomedical applications
Fibroblasts
Genetic engineering
hydrogels
Immune system
Materials science
Modularity
Spheroids
Stability
Tissue engineering
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Summary: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 (Controlled Apoptosis in Multicellular tissues for Engineered Organogenesis) 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. 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.
ISSN:1616-301X
1616-3028
DOI:10.1002/adfm.201910442