TY - JOUR
T1 - Gradients in the in vivo intestinal stem cell compartment and their in vitro recapitulation in mimetic platforms
AU - Malijauskaite, Sigita
AU - Connolly, Sinead
AU - Newport, David
AU - McGourty, Kieran
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - ASCs
KW - Biomechanics of soft tissue
KW - ECM
KW - Enteroids
KW - ISCs
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=85104129443&partnerID=8YFLogxK
U2 - 10.1016/j.cytogfr.2021.03.002
DO - 10.1016/j.cytogfr.2021.03.002
M3 - Review article
C2 - 33858768
AN - SCOPUS:85104129443
SN - 1359-6101
VL - 60
SP - 76
EP - 88
JO - Cytokine and Growth Factor Reviews
JF - Cytokine and Growth Factor Reviews
ER -