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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.
Sec. Organoids and Organ-On-A-Chip
Volume 12 - 2024 | doi: 10.3389/fbioe.2024.1506976

Fibroblasts modulate epithelial cell behavior within the proliferative niche and differentiated cell zone within a human colonic crypt model

Provisionally accepted
Angelo Massaro Angelo Massaro Cecilia Villegas Novoa Cecilia Villegas Novoa Yuli Wang Yuli Wang Nancy Allbritton Nancy Allbritton *
  • University of Washington, Seattle, United States

The final, formatted version of the article will be published soon.

    Colonic epithelium is situated above a layer of fibroblasts that provide supportive factors for stem cells at the crypt base and promote differentiation of cells in the upper crypt and luminal surface. To study the fibroblast-epithelial cell interactions, an in vitro crypt model was formed on a shaped collagen scaffold with primary epithelial cells growing above a layer of primary colonic fibroblasts. The crypts possessed a basal stem cell niche populated with proliferative cells and a differentiated, nondividing cell zone at the luminal crypt end. The presence of fibroblasts enhanced cell differentiation and accelerated the rate at which a high resistance epithelial cell layer formed relative to cultures without fibroblasts. The fibroblasts modulated cell proliferation within crypts increasing the number of crypts populated with proliferative cells but decreasing the total number of proliferative cells in each crypt. Bulk-RNA sequencing revealed 41 genes that were significantly upregulated and 190 genes that were significantly downregulated in cocultured epithelium relative to epithelium cultured without fibroblasts. This epithelium-fibroblast crypt model suggests bidirectional communication between the two cell types and has the potential to serve as a model to investigate fibroblast-epithelial cell interactions in health and disease.

    Keywords: colon crypt, Epithelial Cells, microphysiological system, organ-on-chip, Large intestine, pericryptal fibroblasts

    Received: 06 Oct 2024; Accepted: 22 Nov 2024.

    Copyright: © 2024 Massaro, Villegas Novoa, Wang and Allbritton. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Nancy Allbritton, University of Washington, Seattle, United States

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