The Sheep as a Large Animal Model for the Investigation and Treatment of Human Disorders

Abstract

An essential aim of biomedical research is to translate basic science information obtained from preclinical research using small and large animal models into clinical practice for the benefit of humans. Research on rodent models has enhanced our understanding of complex pathophysiology, thus providing potential translational pathways. However, the success of translating drugs from pre-clinical to clinical therapy has been poor, partly due to the choice of experimental model. The sheep model, in particular, is being increasingly applied to the field of biomedical research and is arguably one of the most influential models of human organ systems. It has provided essential tools and insights into cardiovascular disorder, orthopaedic examination, reproduction, gene therapy, and new insights into neurodegenerative research. Unlike the widely adopted rodent model, the use of the sheep model has an advantage over improving neuroscientific translation, in particular due to its large body size, gyrencephalic brain, long lifespan, more extended gestation period, and similarities in neuroanatomical structures to humans. This review aims to summarise the current status of sheep to model various human diseases and enable researchers to make informed decisions when considering sheep as a human biomedical model.

Repair of Long Nerve Defects with a New Decellularized Nerve Graft in Rats and in Sheep

“…Hence, standardized models of long nerve gap injury in large animals are necessary to evaluate tolerability and efficacy of new treatment strategies for severe nerve injuries [ 6 ]. In this sense, sheep are proposed as an optimal large animal model, since they have similarities in general body and neural structures to humans [ 37 , 38 ], and particularly peripheral nerve dimensions and structure similar to humans [ 20 , 39 , 40 , 41 ]. Moreover, their calm nature, compared to other large animals used as experimental models, such as pigs, enables easier postoperative management and clinical testing [ 18 , 42 ].…”

Application of the transgenic pig model in biomedical research: A review

“…In addition, with the growing number of potential targeted genes and pathogenesis of human diseases that have been discovered, using gene editing technology to explore functions of the genome, realizing genetic improvement in reproduction traits, and overcoming species differences to simulate human diseases accurately still need further research. Moreover, models of large animals for human diseases have already been developed well in species like sheep ( Banstola and Reynolds, 2022 ), monkeys ( Khampang et al, 2021 ), and horses ( Metrangolo et al, 2021 ) that covered genetic diseases like Batten disease ( Karageorgos et al, 2011 ) and Gaucher disease ( Kawabata et al, 2021 ), hypophyseal dysfunction ( Koch and Betts, 2007 ), joint problems ( Harman et al, 2021 ), and cutaneous wounds ( Rogers, 2016b ). Although the system of a species can differ from another, the ways of creating transgenic pig may provide new directions for other large animal models.…”

Organ‐on‐a‐chip technologies for biomedical research and drug development: A focus on the vasculature

“…22,23 Sheep, as a largeanimal model, shares hemodynamic flow parameters with similar anatomy to the human body and is a standard preclinical model for the testing of the efficacy and safety of new drug formulations and vaccines. 24 Nonhuman primates share biological, clinical, and behavioral (cognitive and societal) features with humans; thus, they are the most vital animal model. 25,26 However, due to the vast amount of similarities, animal welfare considerations within experimentation are the highest in this model.…”

“…Swine models provide a better understanding of human disease models and are an optimal model for xenotransplantation and surgical training as their organs are of similar size to human organs 22,23 . Sheep, as a large‐animal model, shares hemodynamic flow parameters with similar anatomy to the human body and is a standard preclinical model for the testing of the efficacy and safety of new drug formulations and vaccines 24 . Nonhuman primates share biological, clinical, and behavioral (cognitive and societal) features with humans; thus, they are the most vital animal model 25,26 .…”