Gradients in the in vivo intestinal stem cell compartment and their in vitro recapitulation in mimetic platforms

Sigita Malijauskaite, Sinead Connolly, David Newport, Kieran McGourty

Research output: Contribution to journalReview articlepeer-review

Abstract

Intestinal tissue, and specifically its mucosal layer, is a complex and gradient-rich environment. Gradients of soluble factor (BMP, Noggin, Notch, Hedgehog, and Wnt), insoluble extracellular matrix proteins (laminins, collagens, fibronectin, and their cognate receptors), stromal stiffness, oxygenation, and sheer stress induced by luminal fluid flow at the crypt-villus axis controls and supports healthy intestinal tissue homeostasis. However, due to current technological challenges, very few of these features have so far been included in in vitro intestinal tissue mimetic platforms. In this review, the tightly defined and dynamic microenvironment of the intestinal tissue is presented in detail. Additionally, the authors introduce the current state-of-the-art intestinal tissue mimetic platforms, as well as the design drawbacks and challenges they face while attempting to capture the complexity of the intestinal tissue's physiology. Finally, the compositions of an “idealized” mimetic system is presented to guide future developmental efforts.

Original languageEnglish
Pages (from-to)76-88
Number of pages13
JournalCytokine and Growth Factor Reviews
Volume60
DOIs
Publication statusPublished - Aug 2021

Keywords

  • ASCs
  • Biomechanics of soft tissue
  • ECM
  • Enteroids
  • ISCs
  • Tissue engineering

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