Suspended Collagen Hydrogels to Replicate Human Colonic Epithelial Cell Interactions with Immune Cells.

Suspended Collagen Hydrogels to Replicate Human Colonic Epithelial Cell Interactions with Immune Cells.
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DOI:
10.1002/adbi.202200129
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发表时间:
2022-11
期刊:
影响因子:
3.7
通讯作者:
Allbritton, Nancy L.
Allbritton, Nancy L.
中科院分区:
生物学3区
文献类型:
--
作者:
Hinman, Samuel S.;Massaro, Angelo;Wang, Yuli;Sims, Christopher E.;Kim, Raehyun;Allbritton, Nancy L.

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The human colon plays critical roles in fluid and salt absorption and harbors the largest immune compartment. There is widespread need for in vitro models of human colon physiology with its innate immune system. A method is described to produce a cassette with a network of struts supporting a suspended, non-chemically crosslinked collagen hydrogel scaffold compatible with the co-culture of primary gastrointestinal epithelium and migratory inflammatory cells. The epithelial monolayer cultured on the suspended collagen possessed a population of polarized and differentiated cells similar to that present in vivo. This epithelial layer displayed proper barrier function with a TEER ≥1,500 Ω cm2 and an apparent permeability ≤10−5 cm2 s−1. Immune cells plated on the basal face of the scaffold transmigrated over a period of 24 h to the epithelial layer in response to epithelial production of IL-8 induced by luminal stimulation of Clostridium difficile Toxin A. These studies demonstrate that this in vitro platform possesses a functional primary colonic epithelial layer with an immune cell compartment capable of recruitment in response to pro-inflammatory cues coming from the epithelium. A primary human colonic epithelial layer was formed on a non-chemically crosslinked collagen hydrogel suspended on a framework of polyester struts. The hydrogel supported an immune cell compartment capable of responding to pro-inflammatory cues from the epithelium by migration through the hydrogel to interface with the epithelial cells. This platform enables studies of the human colonic epithelium and intestinal immune compartment interface.
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