Application of porcine gastrointestinal organoid units as a potential in vitro tool for drug discovery and development

J Appl Toxicol. 2019 Jan;39(1):4-15. doi: 10.1002/jat.3641. Epub 2018 Jun 11.

Abstract

The gastrointestinal tract (GI) is a crucial part of the body for growth and development and its dysregulation can lead to several diseases with detrimental effects. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. Organoids are three-dimensional self-organizing and self-renewing structures that are composed of a cluster of different cells in vitro that resemble their organ of origin in architecture and function. Over recent years, organoids have been increasingly used to study developmental biology, disease progression, i.e., cancer, tissue engineering and regenerative medicine and other biological processes. Owing to their complex nature and ability to retain the morphological and molecular patterns of their tissue-of-origin, they have great potential as alternative tools/models for drug screening, development and biomarker discovery. Using a species with similar genetic homology to humans as a source of organoids, such as the porcine model may offer huge translational relevance. This review focuses on the culture and establishment of porcine organoid units and their potential use and application as in vitro models to further the science of drug discovery, by overcoming current limitations of established two- and three-dimensional models. It also highlights the translational application of using porcine organoids as a model of different disease contexts.

Keywords: 3-dimensional; biomarker discovery; drug screening; gastrointestinal tract; organoid units; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Pharmacological*
  • Biomedical Research / methods
  • Cells, Cultured / drug effects*
  • Drug Discovery / methods*
  • Drug Evaluation, Preclinical / methods*
  • Gastrointestinal Tract / drug effects*
  • Humans
  • Models, Animal
  • Models, Biological
  • Organoids / drug effects*
  • Swine
  • Tissue Engineering / methods*

Substances

  • Biomarkers, Pharmacological