Organoids: a promising new in vitro platform in livestock and veterinary research

Abstract

Organoids are self-organizing, self-renewing three-dimensional cellular structures that resemble organs in structure and function. They can be derived from adult stem cells, embryonic stem cells, or induced pluripotent stem cells. They contain most of the relevant cell types with a topology and cell-to-cell interactions resembling that of the in vivo tissue. The widespread and increasing adoption of organoid-based technologies in human biomedical research is testament to their enormous potential in basic, translational- and applied-research. In a similar fashion there appear to be ample possibilities for research applications of organoids from livestock and companion animals. Furthermore, organoids as in vitro models offer a great possibility to reduce the use of experimental animals. Here, we provide an overview of studies on organoids in livestock and companion animal species, with focus on the methods developed for organoids from a variety of tissues/organs from various animal species and on the applications in veterinary research. Current limitations, and ongoing research to address these limitations, are discussed. Further, we elaborate on a number of fields of research in animal nutrition, host-microbe interactions, animal breeding and genomics, and animal biotechnology, in which organoids may have great potential as an in vitro research tool.

The Development of Ovine Gastric and Intestinal Organoids for Studying Ruminant Host-Pathogen Interactions

“…The use of stem-cell derived GI organoids or “mini-guts” for farmed livestock species, including ruminants, is an exciting recent development that promises to provide a physiologically relevant and host-specific in vitro cell culture system to interrogate host-pathogen interactions ( Beaumont et al., 2021 ; Kar et al., 2021 ). A recent study has demonstrated the feasibility of generating organoids from bovine ileum tissue with the derived organoids expressing genes associated with intestinal epithelia cell types ( Hamilton et al., 2018 ).…”

Generation of equine enteroids and enteroid-derived 2D monolayers that are responsive to microbial mimics

“…While enteroid cultures are starting to become standardized in human and mouse [ 3 ], there are less studies published on enteroids from farm animals as recently reviewed [ 4 , 5 ] and only two studies describing equine enteroids [ 6 , 7 ]. Several of the horse’s most common diseases are linked to the gastro-intestinal tract, such as colic, laminitis, diarrhoea and parasite infections.…”

Harness Organoid Models for Virological Studies in Animals: A Cross-Species Perspective

“…Organoids bridge the gap between 2D cell culture and animal models by providing a culturable system; this allows manipulation of cell cultures while representing better mimicking of in vivo cellularity and physiology ( Lehmann et al, 2019 ; Kim et al, 2020 ). As implicated in several pilot studies and eminent reviews, we emphasize that cross-species investigation of organoid cultures in domestic and wild animals, will significantly promote virology studies, particularly for efficiently validating the infection loop of epizootic and zoonotic viruses in different animal species, including humans ( Barrila et al, 2018 ; Ramani et al, 2018 ; Lehmann et al, 2019 ; Montes-Olivas et al, 2019 ; Bar-Ephraim et al, 2020 ; Duque-Correa et al, 2020 ; Kim et al, 2020 ; Schutgens and Clevers, 2020 ; Sridhar et al, 2020 ; Yuki et al, 2020 ; Hofer and Lutolf, 2021 ; Kar et al, 2021 ; Pain, 2021 ).…”

“…As demonstrated from a variety of pioneering studies, organoid technology can be adopted in most vertebrate species to retain its strength in modeling animal diseases; this is particularly true in the case of the microbe-host interaction in infectious cases ( Barrila et al, 2018 ; Ramani et al, 2018 ; Montes-Olivas et al, 2019 ; Bar-Ephraim et al, 2020 ; Duque-Correa et al, 2020 ; Schutgens and Clevers, 2020 ; Sridhar et al, 2020 ; Yuki et al, 2020 ). In this regard, tissue/organ resources are readily available for establishing organoid culture, particularly in livestock animals; this also addresses the concerns of animal welfare, reducing the number of animals that may succumb to experimentally pathogenic infections and disease modeling ( Kar et al, 2021 ; Pain, 2021 ). Organoid-relevant studies have been boosted among animals in the last 10 years ( Derricott et al, 2019 ; Corrò et al, 2020 ; Seeger, 2020 ; Beaumont et al, 2021 ; Bourdon et al, 2021 ; Kar et al, 2021 ; Pain, 2021 ), with multiple studies using organoids to promote COVID-19 investigation ( Clevers, 2020 ; Monteil et al, 2020 ; Yang et al, 2020 ; Han et al, 2021 ).…”