Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Modeling disease using three dimensional cell culture: multi-lumen and inverted cyst phenotypes
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Three-dimensional cell culture provides a unique system to investigate intrinsic mechanisms and micro environmental cues involved in the morphogenesis of epithelial glandular architectures. While this culture system allows insight into normal tissue development, it is also is readily amenable to manipulations that permit cellular modeling of various disease states. Here, we discuss a range of cellular and genetic alterations that result in two distinct cyst phenotypes, the multi-lumen cyst and the inverted cyst, both of which involve defects in cell polarity and lumen formation. Multi-lumen cyst formation results from disturbances in the mechanisms that regulate cell polarity, apical assembly, and the rate of lumen clearance. In the inverted cyst, the apical domain is oriented adjacent to the matrix, markedly affecting the morphogenic cues the matrix provides for cystogenesis. Both of these abnormal glandular phenotypes are highly reminiscent of histological patterns used to classify a number of diseases. A better understanding of the causes of multi-lumen and inverted cysts will provide insights into the origin and progression of epithelial diseases, potentially leading to the development of new therapies.