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The Organoid Reconstitution Assay ORA for the Functional Analysis of Intestinal Stem and Niche Cells
Published on: November 20, 2017
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Bioengineered Systems and Designer Matrices That Recapitulate the Intestinal Stem Cell Niche.
Yuli Wang1, Raehyun Kim2, Samuel S Hinman1
1Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina.
Cellular and Molecular Gastroenterology and Hepatology
|April 21, 2018
Summary
Intestinal stem cells (ISCs) rely on niche gradients for renewal. Bioengineered models now mimic these gradients to study ISC behavior and develop new therapies.
Area of Science:
- Gastroenterology
- Stem Cell Biology
- Bioengineering
Background:
- Intestinal stem cells (ISCs) are crucial for maintaining the epithelial barrier through continuous self-renewal and differentiation.
- The ISC niche, located at the crypt base, provides essential factors that diminish along the crypt-villus axis.
- Epithelial cells have a short lifespan (approx. 7 days) and are constantly replenished by ISCs.
Purpose of the Study:
- To review the evidence for in vivo niche gradients influencing intestinal epithelial renewal.
- To discuss the application of bioengineered in vitro models in recapitulating these gradients.
- To highlight advancements in tissue engineering for research and clinical applications.
Main Methods:
- Review of existing literature on ISC niche factors and gradients.
- Discussion of bioengineered tools and platforms, including organ-on-chip and microfluidic devices.
- Integration of primary intestinal epithelial cells with biomimetic platforms.
Main Results:
- In vivo gradients of growth factors, extracellular matrix, bacterial products, gases, and stiffness are critical for ISC function.
- Bioengineered platforms can successfully recapitulate key aspects of these gradients.
- These models enable the study of normal physiology and disease states in vitro.
Conclusions:
- Bioengineered models are increasingly sophisticated in mimicking the ISC niche.
- These advanced models facilitate basic science research, drug screening, and personalized medicine.
- Understanding and recreating niche gradients are vital for developing high-fidelity intestinal tissue constructs.
Keywords:
3D, 3-dimensionalBMP, Bone morphogenetic proteinBioengineeringECM, extracellular matrixEph, erythropoietin-producing human hepatocellular receptorEphrin, Eph family receptor interacting proteinsGradientsIFN-γ, interferon-γISC, intestinal stem cellIntestinal Epithelial CellsNO, nitric oxideSFCA, short-chain fatty acidsStem Cell NicheTA, transit amplifyingWnt, wingless-related integration siteRelated Concept Videos
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