Farm and Companion Animal Organoid Models in Translational Research: A Powerful Tool to Bridge the Gap Between Mice and Humans

Abstract

Animal organoid models derived from farm and companion animals have great potential to contribute to human health as a One Health initiative, which recognize a close inter-relationship among humans, animals and their shared environment and adopt multi-and trans-disciplinary approaches to optimize health outcomes. With recent advances in organoid technology, studies on farm and companion animal organoids have gained more attention in various fields including veterinary medicine, translational medicine and biomedical research. Not only is this because three-dimensional organoids possess unique characteristics from traditional two-dimensional cell cultures including their self-organizing and self-renewing properties and high structural and functional similarities to the originating tissue, but also because relative to conventional genetically modified or artificially induced murine models, companion animal organoids can provide an excellent model for spontaneously occurring diseases which resemble human diseases. These features of companion animal organoids offer a paradigm-shifting approach in biomedical research and improve translatability of in vitro studies to subsequent in vivo studies with spontaneously diseased animals while reducing the use of conventional animal models prior to human clinical trials. Farm animal organoids also could play an important role in investigations of the pathophysiology of zoonotic and reproductive diseases by contributing to public health and improving agricultural production. Here, we discuss a brief history of organoids and the most recent updates on farm and companion animal organoids, followed by discussion on their potential in public health, food security, and comparative medicine as One Health initiatives. We highlight recent evolution in the culturing of organoids and their integration with organ-on-a-chip systems to overcome current limitations in in vitro studies. We envision multidisciplinary work integrating organoid culture and organ-on-a-chip technology can contribute to improving both human and animal health.

Keywords: One Health; animal organoid; comparative medicine; public health; translational research.

Figure 1

Comparisons of the key features of the 3D organoid culture system, organoid-derived 2D monolayer culture system, and organ-on-a-chip system. The 3D organoids should be derived from the relevant donors to develop the cell culture system that can be established efficiently and passaged readily while maintaining the physiologic cell diversity. To accomplish more advanced epithelial interface investigation, organoid-derived 2D monolayer can be established using conventional Transwell system or other well established 2D culture systems. Integration of the 3D organoid culture system and organ-on-a-chip technologies provides the most suitable system to investigate more complex microenvironment with host cells and microbial cells because of its dynamic environment with mechanical motions and the ability to manipulate the oxygen gradient within the system. Created with BioRender.com.

Figure 2

One Health initiatives with the integration of animal organoids and organ-on-a-chip technologies. Integration of animal organoids and organ-on-a-chip technologies will allow translational research (i.e., bench to bedside research) in various animal species and humans to enable cross-species investigation of physiology in health and disease. This allows the application of these technologies to comparative research and potentially efficient drug discovery with the use of natural animal disease models because of the similar environment, diet, and disease development that they share with humans. Investigations of host-pathogen interactions in zoonotic infectious diseases using animal organoids can improve public health through translational research as some animals only develop mild clinical diseases or serve as asymptomatic carriers upon exposure to potential pathogens which can cause severe clinical diseases in humans. Further mechanistic and novel therapeutic investigations in various pathogenic and wasting diseases (i.e., enteric pathogens) or reproductive diseases can be performed with translational medicine using farm animal organoids, which could ultimately contribute to improve the agricultural production to meet ever-growing human needs. Created with BioRender.com.