Human Microphysiological Models of Intestinal Tissue and Gut Microbiome

Overview

Journal Front Bioeng Biotechnol

Date 2020 Aug 28

PMID 32850690

Citations 20

Authors

Steven N Steinway

Jad Saleh

Bon-Kyoung Koo

Delphine Delacour

Deok-Ho Kim

Affiliations

Soon will be listed here.

Abstract

The gastrointestinal (GI) tract is a complex system responsible for nutrient absorption, digestion, secretion, and elimination of waste products that also hosts immune surveillance, the intestinal microbiome, and interfaces with the nervous system. Traditional systems cannot harness the architectural and functional complexity of the GI tract. Recent advances in organoid engineering, microfluidic organs-on-a-chip technology, and microfabrication allows us to create better models of human organs/tissues. These micro-physiological systems could integrate the numerous cell types involved in GI development and physiology, including intestinal epithelium, endothelium (vascular), nerve cells, immune cells, and their interplay/cooperativity with the microbiome. In this review, we report recent progress in developing micro-physiological models of the GI systems. We also discuss how these models could be used to study normal intestinal physiology such as nutrient absorption, digestion, and secretion as well as GI infection, inflammation, cancer, and metabolism.

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References

Sharkey K, Beck P, McKay D . Neuroimmunophysiology of the gut: advances and emerging concepts focusing on the epithelium. Nat Rev Gastroenterol Hepatol. 2018; 15(12):765-784. DOI: 10.1038/s41575-018-0051-4. View

Kim H, Ingber D . Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation. Integr Biol (Camb). 2013; 5(9):1130-40. DOI: 10.1039/c3ib40126j. View

Petrey A, de la Motte C . The extracellular matrix in IBD: a dynamic mediator of inflammation. Curr Opin Gastroenterol. 2017; 33(4):234-238. PMC: 5562400. DOI: 10.1097/MOG.0000000000000368. View

He J, Guo H, Zheng W, Yao W . Effects of Stress on the Mucus-microbial Interactions in the Gut. Curr Protein Pept Sci. 2018; 20(2):155-163. DOI: 10.2174/1389203719666180514152406. View

Pocock K, Delon L, Bala V, Rao S, Priest C, Prestidge C . Intestine-on-a-Chip Microfluidic Model for Efficient in Vitro Screening of Oral Chemotherapeutic Uptake. ACS Biomater Sci Eng. 2021; 3(6):951-959. DOI: 10.1021/acsbiomaterials.7b00023. View

Maghsoudlou P, Totonelli G, Loukogeorgakis S, Eaton S, De Coppi P . A decellularization methodology for the production of a natural acellular intestinal matrix. J Vis Exp. 2013; (80). PMC: 3923547. DOI: 10.3791/50658. View

Finkbeiner S, Freeman J, Wieck M, El-Nachef W, Altheim C, Tsai Y . Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoids. Biol Open. 2015; 4(11):1462-72. PMC: 4728347. DOI: 10.1242/bio.013235. View

Baptista D, Teixeira L, van Blitterswijk C, Giselbrecht S, Truckenmuller R . Overlooked? Underestimated? Effects of Substrate Curvature on Cell Behavior. Trends Biotechnol. 2019; 37(8):838-854. DOI: 10.1016/j.tibtech.2019.01.006. View

Shin W, Kim H . Intestinal barrier dysfunction orchestrates the onset of inflammatory host-microbiome cross-talk in a human gut inflammation-on-a-chip. Proc Natl Acad Sci U S A. 2018; 115(45):E10539-E10547. PMC: 6233106. DOI: 10.1073/pnas.1810819115. View

10.

Simon-Assmann P, Kedinger M, DE ARCANGELIS A, Rousseau V, Simo P . Extracellular matrix components in intestinal development. Experientia. 1995; 51(9-10):883-900. DOI: 10.1007/BF01921739. View

11.

Heo I, Dutta D, Schaefer D, Iakobachvili N, Artegiani B, Sachs N . Modelling Cryptosporidium infection in human small intestinal and lung organoids. Nat Microbiol. 2018; 3(7):814-823. PMC: 6027984. DOI: 10.1038/s41564-018-0177-8. View

12.

Jung P, Sato T, Merlos-Suarez A, Barriga F, Iglesias M, Rossell D . Isolation and in vitro expansion of human colonic stem cells. Nat Med. 2011; 17(10):1225-7. DOI: 10.1038/nm.2470. View

13.

Totonelli G, Maghsoudlou P, Garriboli M, Riegler J, Orlando G, Burns A . A rat decellularized small bowel scaffold that preserves villus-crypt architecture for intestinal regeneration. Biomaterials. 2012; 33(12):3401-10. PMC: 4022101. DOI: 10.1016/j.biomaterials.2012.01.012. View

14.

Wang Y, Gunasekara D, Reed M, DiSalvo M, Bultman S, Sims C . A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium. Biomaterials. 2017; 128:44-55. PMC: 5392043. DOI: 10.1016/j.biomaterials.2017.03.005. View

15.

Forbester J, Goulding D, Vallier L, Hannan N, Hale C, Pickard D . Interaction of Salmonella enterica Serovar Typhimurium with Intestinal Organoids Derived from Human Induced Pluripotent Stem Cells. Infect Immun. 2015; 83(7):2926-34. PMC: 4468523. DOI: 10.1128/IAI.00161-15. View

16.

Jung K, Lee H, Son Y, Lee M, Kim Y, Oh S . Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids. Nat Commun. 2018; 9(1):3039. PMC: 6072745. DOI: 10.1038/s41467-018-05450-8. View

17.

Chassaing B, Aitken J, Malleshappa M, Vijay-Kumar M . Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol. 2014; 104:15.25.1-15.25.14. PMC: 3980572. DOI: 10.1002/0471142735.im1525s104. View

18.

de Haan P, Ianovska M, Mathwig K, van Lieshout G, Triantis V, Bouwmeester H . Digestion-on-a-chip: a continuous-flow modular microsystem recreating enzymatic digestion in the gastrointestinal tract. Lab Chip. 2019; 19(9):1599-1609. DOI: 10.1039/c8lc01080c. View

19.

Martignoni M, Groothuis G, de Kanter R . Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol. 2006; 2(6):875-94. DOI: 10.1517/17425255.2.6.875. View

20.

Maurer M, Gresnigt M, Last A, Wollny T, Berlinghof F, Pospich R . A three-dimensional immunocompetent intestine-on-chip model as in vitro platform for functional and microbial interaction studies. Biomaterials. 2019; 220:119396. DOI: 10.1016/j.biomaterials.2019.119396. View