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Title: 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 significant advance for tissue engineering. In this work, a new method, entitled CAMEO (ControlledApoptosis inMulticellular tissues forEngineeredOrganogenesis) 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.

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Author(s) / Creator(s):
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Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Advanced Functional Materials
Medium: X
Sponsoring Org:
National Science Foundation
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    This article was corrected on 18 July 2022. See the end of the full text for details.

    Basic Protocol 1: Uniaxial PCL electrospinning

    Basic Protocol 2: Coaxial electrospinning

    Support Protocol 1: Scaffold characterization for Basic Protocols 1 and 2

    Basic Protocol 3: Cell seeding on uniaxial and coaxial electrospun scaffolds and MTS assay

    Support Protocol 2: Preparation of scaffold with cells for scanning electron microscopy

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