International Journal of Molecular Sciences · 19 authors, 9 centres
This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.
This review summarizes the development and applications of adult stem cell-derived organoids from various animal species, highlighting their potential in reverse translational research under the One Health Initiative. Canine organoids are identified as particularly promising for bridging veterinary and human medicine due to shared environmental and lifestyle factors. The paper emphasizes the need for standardization and data sharing to advance the field.
**Background:** Preclinical biomedical research is limited by the predictiveness of in vivo and in vitro models. In vivo models, while complex, face ethical, financial, and experimental constraints. Traditional 2D cell lines, such as Caco-2, cannot fully simulate the complexity of healthy epithelium, lacking key cell types and metabolic machinery. The One Health Initiative promotes knowledge sharing between human, animal, and environmental health, while reverse translational research allows data from veterinary and human clinical research to be shared. Organoid technology, particularly adult stem cell-derived (AdSC) organoids, offers three-dimensional multicellular constructs that reliably mimic organ microanatomy and physiology. Since the first murine intestinal organoids were described in 2009, organoids have been derived from numerous species, including humans, rodents, and traditional veterinary and exotic animals.
**Methods:** This is a narrative review summarizing the literature on AdSC-derived organoids from animal species, with a focus on their applications in reverse translational research. The authors performed a PubMed search on 14 November 2022, using terms such as "organoid* AND (canine OR equine OR feline OR horse* OR dogs OR cats)", yielding 460 results. Selection was further confined to adult stem cell-derived organoids dependent on stem cell markers or Wnt signaling, and limited to the first occurrence of organ and animal organoid line development. The review covers organoids from intestinal, liver, renal, pancreatic, skin, corneal, and venom gland tissues, among others.
**Key Results:** The review describes the successful establishment of organoids from numerous species, including canine, feline, equine, bovine, porcine, ovine, galline, rabbit, monkey, and snake. Key findings include: - Canine intestinal organoids were first described in 2019 and have been used for drug permeability studies, host-pathogen interactions, and disease modeling. They can be grown as 2D monolayers on permeable supports, with standardized protocols published in 2022. - Feline hepatic organoids were developed in 2017 and used to model hepatic steatosis, showing lipid accumulation in response to free fatty acids and sensitivity to drugs like etomoxir and L-carnitine. - Equine endometrial organoids were derived in 2020, including from the endangered Przewalski's horse, and showed hormonal responsiveness. - Snake venom gland organoids were first described in 2020, producing venom peptides that reflect crude venom composition and biological activity, offering a potential alternative to venom milking. - Bat intestinal organoids were established in 2020-2021 and shown to be susceptible to SARS-CoV-2 and Pteropine orthoreovirus. - Canine corneal organoids were first reported in 2022, representing the first adult stem cell-derived corneal organoids in any species. - The review notes that many organoid lines require Wnt pathway activation (e.g., via R-spondin) and that growth factors like EGF and Noggin are commonly used. Reproducibility challenges include lack of standardization and batch-to-batch variability in hydrogels like Matrigel.
**Clinical Implications:** Animal-derived organoids, particularly from companion animals like dogs, offer significant potential for reverse translational research, allowing knowledge to flow between veterinary and human medicine. Canine organoids can be used for drug permeability and toxicity testing, personalized medicine, and studying diseases that naturally occur in dogs, such as inflammatory bowel disease and cancer. Feline hepatic organoids provide a model for hepatic steatosis, a condition to which cats are predisposed. Snake venom gland organoids could revolutionize antivenom production by providing a safer, more consistent source of venom. The One Health approach, facilitated by organoid technology, can improve both human and animal health by leveraging unique adaptations across species. However, standardization of protocols and data sharing are critical for advancing the field.