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Human mini-guts: new insights into intestinal physiology and host-pathogen interactions
Julie G In1, Jennifer Foulke-Abel1, Mary K Estes2
1Department of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, Maryland 21205, USA.
Nature Reviews. Gastroenterology & Hepatology
|September 29, 2016
Summary
Human mini-guts, or enteroids, derived from intestinal stem cells, offer a functional model for studying gastrointestinal transport and diseases. This advance overcomes limitations of animal models for developing new therapies.
Area of Science:
- Gastroenterology
- Stem Cell Biology
- Physiology
Background:
- Human intestinal stem cells (LGR5+) can be cultured to form self-renewing "mini-guts" (enteroids/colonoids).
- These models mimic the in vivo crypt-villus architecture and cellular diversity of the human intestine.
- Existing models using animals or cancer cell lines have limitations in studying intestinal physiology and pathophysiology.
Purpose of the Study:
- To review the characterization of human mini-guts as a physiological model.
- To highlight their utility in studying intestinal transport and host-pathogen interactions.
- To underscore their potential for developing new therapies for enteric infections.
Main Methods:
- Isolation of LGR5+ intestinal stem cells from human small intestine or colon.
- Culture of stem cells with WNT3A and other growth factors to promote stemness and differentiation.
- Characterization of the resulting enteroids/colonoids for physiological function and cellular composition.
Main Results:
- Human mini-guts exhibit indefinite propagation and develop a functional crypt-villus axis.
- They differentiate into all major intestinal epithelial cell types, enabling detailed physiological studies.
- These models allow for specific functional studies of secretion and absorption in different intestinal segments.
Conclusions:
- Human mini-guts represent a significant advancement over animal or cancer cell line models for gastrointestinal research.
- They provide a unique platform for investigating intestinal transport, pathophysiology, and host-pathogen interactions.
- This model holds promise for the development of novel therapeutic strategies for acute enteric infections.
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