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

[Display omitted] • Intestinal crypt-villus microenvironment is rich with various gradients. • Due to its complexity the current in vitro models fail to accurately recapitulate all of its parameters. • Spatial distribution of various gradients at the crypt-villus axis are the key drivers of intestinal tissue homeostasis. • Crypt-villus axis requires comprehensive characterization to improve current state-of-the-art intestinal tissue models. 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. [ABSTRACT FROM AUTHOR]