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Engineering epithelial-stromal interactions in vitro for toxicology assessment
Belair, D. AND B. Abbott. Engineering epithelial-stromal interactions in vitro for toxicology assessment. TOXICOLOGY. Elsevier Science Ltd, New York, NY, , 93-107, (2017).
The purpose of this review is to highlight advances in tissue engineering that might enable the bioengineering of human embryonic tissues in a dish. Traditional approaches for developmental toxicity assessment use animal models and tissue explants that are difficult and expensive to source, low throughput, and may not capture the key aspects of human development. This leaves many putative toxicants un-tested for their influence on human developmental processes. Bioengineering approaches to mimic human developmental processes in a dish may enable more rapid developmental toxicity assessment in vitro. In this review, we focus on describing the bioengineering approaches that have been taken to mimic mature human epithelial tissues in vitro by leveraging stromal-epithelial interactions, and we discuss how similar bioengineering approaches could be used to model developmental processes that are dependent on stromal-epithelial interactions including heart tube closure, neural tube closure, palatal fusion, and genital tubercle development. This review aims to introduce the reader to how bioengineering can be used to improve the speed and efficiency of developmental toxicity assessment using models of human morphogenetic fusion in vitro.
Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo tissue recombination, and in vitro co-cultures. Although these approaches have elucidated signaling mechanisms underlying morphogenetic processes and adult mammalian epithelial tissue function, they are limited by the availability of human tissue, low throughput, and human developmental or physiological relevance. Objectives: Bioengineering strategies to promote EMIs using human epithelial and mesenchymal cells have enabled the development of human in vitro models of adult epidermal and glandular tissues. In this review, we describe recent bioengineered models of human epithelial tissue and organs that can instruct the design of organotypic models of human developmental processes.Methods: We reviewed current bioengineering literature and here describe how bioengineered EMIs have enabled the development of human in vitro epithelial tissue models.Discussion: Engineered models to promote EMIs have recapitulated the architecture, phenotype, and function of adult human epithelial tissue, and similar engineering principles could be used to develop models of developmental morphogenesis. We describe how bioengineering strategies including bioprinting and spheroid culture could be implemented to design organotypic human in vitro models of morphogenetic processes including palate fusion. Conclusion: Organotypic culture models of human morphogenetic processes could reduce reliance on costly and low throughput animal studies for developmental toxicity assessment and could achieve the throughput necessary to screen for toxicants that inhibit either mature tissue function or developmental morphogenesis in vitro.