A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium

Yuli Wang, Dulan B. Gunasekara, Mark I. Reed, Matthew DiSalvo, Scott J. Bultman, Christopher E. Sims, Scott T. Magness, Nancy L. Allbritton

Research output: Contribution to journalArticle

  • 18 Citations

Abstract

The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors. In the current work, we report the development of a micropatterned collagen scaffold with suitable extracellular matrix and stiffness to generate an in vitro self-renewing human small intestinal epithelium that replicates key features of the in vivo small intestine: a crypt-villus architecture with appropriate cell-lineage compartmentalization and an open and accessible luminal surface. Chemical gradients applied to the crypt-villus axis promoted the creation of a stem/progenitor-cell zone and supported cell migration along the crypt-villus axis. This new approach combining microengineered scaffolds, biophysical cues and chemical gradients to control the intestinal epithelium ex vivo can serve as a physiologically relevant mimic of the human small intestinal epithelium, and is broadly applicable to model other tissues that rely on gradients for physiological function.

LanguageEnglish (US)
Pages44-55
Number of pages12
JournalBiomaterials
Volume128
DOIs
StatePublished - Jun 1 2017

Fingerprint

Intestinal Mucosa
Scaffolds (biology)
Collagen
Scaffolds
Tissue
Stem cells
Intercellular Signaling Peptides and Proteins
Stem Cells
Stiffness
Cell Lineage
Small Intestine
Cell Movement
Cues
Extracellular Matrix
In Vitro Techniques

Keywords

  • Crypt
  • Intestine
  • Microfabrication
  • Scaffold
  • Stem cell
  • Villus

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium. / Wang, Yuli; Gunasekara, Dulan B.; Reed, Mark I.; DiSalvo, Matthew; Bultman, Scott J.; Sims, Christopher E.; Magness, Scott T.; Allbritton, Nancy L.

In: Biomaterials, Vol. 128, 01.06.2017, p. 44-55.

Research output: Contribution to journalArticle

@article{8f80cc14d91544aa93254af8db96d946,
title = "A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium",
abstract = "The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors. In the current work, we report the development of a micropatterned collagen scaffold with suitable extracellular matrix and stiffness to generate an in vitro self-renewing human small intestinal epithelium that replicates key features of the in vivo small intestine: a crypt-villus architecture with appropriate cell-lineage compartmentalization and an open and accessible luminal surface. Chemical gradients applied to the crypt-villus axis promoted the creation of a stem/progenitor-cell zone and supported cell migration along the crypt-villus axis. This new approach combining microengineered scaffolds, biophysical cues and chemical gradients to control the intestinal epithelium ex vivo can serve as a physiologically relevant mimic of the human small intestinal epithelium, and is broadly applicable to model other tissues that rely on gradients for physiological function.",
keywords = "Crypt, Intestine, Microfabrication, Scaffold, Stem cell, Villus",
author = "Yuli Wang and Gunasekara, {Dulan B.} and Reed, {Mark I.} and Matthew DiSalvo and Bultman, {Scott J.} and Sims, {Christopher E.} and Magness, {Scott T.} and Allbritton, {Nancy L.}",
year = "2017",
month = "6",
day = "1",
doi = "10.1016/j.biomaterials.2017.03.005",
language = "English (US)",
volume = "128",
pages = "44--55",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium

AU - Wang,Yuli

AU - Gunasekara,Dulan B.

AU - Reed,Mark I.

AU - DiSalvo,Matthew

AU - Bultman,Scott J.

AU - Sims,Christopher E.

AU - Magness,Scott T.

AU - Allbritton,Nancy L.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors. In the current work, we report the development of a micropatterned collagen scaffold with suitable extracellular matrix and stiffness to generate an in vitro self-renewing human small intestinal epithelium that replicates key features of the in vivo small intestine: a crypt-villus architecture with appropriate cell-lineage compartmentalization and an open and accessible luminal surface. Chemical gradients applied to the crypt-villus axis promoted the creation of a stem/progenitor-cell zone and supported cell migration along the crypt-villus axis. This new approach combining microengineered scaffolds, biophysical cues and chemical gradients to control the intestinal epithelium ex vivo can serve as a physiologically relevant mimic of the human small intestinal epithelium, and is broadly applicable to model other tissues that rely on gradients for physiological function.

AB - The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors. In the current work, we report the development of a micropatterned collagen scaffold with suitable extracellular matrix and stiffness to generate an in vitro self-renewing human small intestinal epithelium that replicates key features of the in vivo small intestine: a crypt-villus architecture with appropriate cell-lineage compartmentalization and an open and accessible luminal surface. Chemical gradients applied to the crypt-villus axis promoted the creation of a stem/progenitor-cell zone and supported cell migration along the crypt-villus axis. This new approach combining microengineered scaffolds, biophysical cues and chemical gradients to control the intestinal epithelium ex vivo can serve as a physiologically relevant mimic of the human small intestinal epithelium, and is broadly applicable to model other tissues that rely on gradients for physiological function.

KW - Crypt

KW - Intestine

KW - Microfabrication

KW - Scaffold

KW - Stem cell

KW - Villus

UR - http://www.scopus.com/inward/record.url?scp=85014819091&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014819091&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2017.03.005

DO - 10.1016/j.biomaterials.2017.03.005

M3 - Article

VL - 128

SP - 44

EP - 55

JO - Biomaterials

T2 - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -