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AAPS J. 2017 Dec 12;20(1):17. doi: 10.1208/s12248-017-0178-1.

Intestinal Stem Cells to Advance Drug Development, Precision, and Regenerative Medicine: A Paradigm Shift in Translational Research.

Author information

1
Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, 2448 Lloyd, 1809 S Riverside Dr., Ames, Iowa, 50011-1250, USA. jmochel@iastate.edu.
2
Department of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, 50011-1250 Ames, Iowa, USA.
3
Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, 78712, USA.
4
Department of Pediatrics, University of California Los Angeles, California, Los Angeles, 90095-1782, USA.

Abstract

Recent advances in our understanding of the intestinal stem cell niche and the role of key signaling pathways on cell growth and maintenance have allowed the development of fully differentiated epithelial cells in 3D organoids. Stem cell-derived organoids carry significant levels of proteins that are natively expressed in the gut and have important roles in drug transport and metabolism. They are, therefore, particularly relevant to study the gastrointestinal (GI) absorption of oral medications. In addition, organoids have the potential to serve as a robust preclinical model for demonstrating the effectiveness of new drugs more rapidly, with more certainty, and at lower costs compared with live animal studies. Importantly, because they are derived from individuals with different genotypes, environmental risk factors and drug sensitivity profiles, organoids are a highly relevant screening system for personalized therapy in both human and veterinary medicine. Lastly, and in the context of patient-specific congenital diseases, orthotopic transplantation of engineered organoids could repair and/or replace damaged epithelial tissues reported in various GI diseases, such as inflammatory bowel disease, cystic fibrosis, and tuft enteropathy. Ongoing translational research on organoids derived from dogs with naturally occurring digestive disorders has the potential to improve the predictability of preclinical models used for optimizing the therapeutic management of severe chronic enteropathies in human patients.

KEYWORDS:

dog; enteropathies; organoid; precision medicine; transplantation

PMID:
29234895
PMCID:
PMC6044282
DOI:
10.1208/s12248-017-0178-1
[Indexed for MEDLINE]
Free PMC Article

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