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.
Highlights
Recent advances in biomedical research have allowed the development of intestinal stem cells in three-dimensional (3D) culture systems supporting ex vivo epithelial growth into organoids [1, 2]
Organoids are a powerful mechanistic tool for identifying molecular targets that are relevant to the pathogenesis of chronic intestinal diseases
The hope is that this Commentary will stimulate support for the research needed to enable organoids to serve as a tool guiding medical decisions within the clinical setting
Summary
Recent advances in biomedical research have allowed the development of intestinal stem cells in three-dimensional (3D) culture systems supporting ex vivo epithelial growth into organoids [1, 2]. Stem cell-derived organoids have multiple advantages over traditional 2D epithelial systems utilizing cancer-derived cell lines (e.g., Caco-2, T84, and HT29) [3], or spontaneously immortalized epithelial cells The present Commentary provides a review of the current knowledge on the biology of intestinal organoids, their potential value in drug discover, precision medicine and regenerative (i.e., transplantation medicine), and the.
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