Synthetic small intestinal scaffolds for improved studies of intestinal differentiation

Cait M. Costello, Hongpeng Jia, Shahab Shaffiey, Jiajie Yu, Nina K. Jain, David Hackam, John C. March

Research output: Contribution to journalArticle

Abstract

In vitro intestinal models can provide new insights into small intestinal function, including cellular growth and proliferation mechanisms, drug absorption capabilities, and host-microbial interactions. These models are typically formed with cells cultured on 2D scaffolds or transwell inserts, but it is widely understood that epithelial cells cultured in 3D environments exhibit different phenotypes that are more reflective of native tissue. Our focus was to develop a porous, synthetic 3D tissue scaffold with villous features that could support the culture of epithelial cell types to mimic the natural microenvironment of the small intestine. We demonstrated that our scaffold could support the co-culture of Caco-2 cells with a mucus-producing cell line, HT29-MTX, as well as small intestinal crypts from mice for extended periods. By recreating the surface topography with accurately sized intestinal villi, we enable cellular differentiation along the villous axis in a similar manner to native intestines. In addition, we show that the biochemical microenvironments of the intestine can be further simulated via a combination of apical and basolateral feeding of intestinal cell types cultured on the 3D models.

Original languageEnglish (US)
Pages (from-to)1222-1232
Number of pages11
JournalBiotechnology and Bioengineering
Volume111
Issue number6
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Scaffolds
Intestines
Cultured Cells
Epithelial Cells
Microbial Interactions
Tissue Scaffolds
Caco-2 Cells
Mucus
Coculture Techniques
Small Intestine
Cell Proliferation
Surface topography
Phenotype
Cell Line
Growth
Cells
Pharmaceutical Preparations
Tissue
In Vitro Techniques

Keywords

  • Caco-2
  • Cadherin
  • Egf
  • Ht29
  • Lysozyme
  • Muc-2

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Medicine(all)

Cite this

Synthetic small intestinal scaffolds for improved studies of intestinal differentiation. / Costello, Cait M.; Jia, Hongpeng; Shaffiey, Shahab; Yu, Jiajie; Jain, Nina K.; Hackam, David; March, John C.

In: Biotechnology and Bioengineering, Vol. 111, No. 6, 2014, p. 1222-1232.

Research output: Contribution to journalArticle

Costello, Cait M. ; Jia, Hongpeng ; Shaffiey, Shahab ; Yu, Jiajie ; Jain, Nina K. ; Hackam, David ; March, John C. / Synthetic small intestinal scaffolds for improved studies of intestinal differentiation. In: Biotechnology and Bioengineering. 2014 ; Vol. 111, No. 6. pp. 1222-1232.
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