Pre-clinical research still relies heavily on in vivo rodent models for studying human conditions. These models continue to be popular with scientists as they are considered to be low-cost with the ability to generate reproducible data quickly. Although neoplastic, inflammatory, knockout and transgenic models have provided a wealth of information regarding the pathogenesis of a range of clinical diseases, they unfortunately fail to mimic the entire pathologic characteristics of the human conditions they are trying to model. Rodents are also typically unsuitable for use with advanced imaging techniques (ultrasound, computed tomography, endoscopy) and translational surgical procedures. Because of these issues, there has been increased interest in the development and use of translational large animal models that more closely approximate the clinical and pathologic features of human diseases.
Various large animal species can be used for translational research. Pigs, and perhaps to a lesser extent sheep, have gained significant scientific attention as they share important proteomic, genomic and immunologic similarities to that of humans. Both species have been used successfully for cardiovascular, respiratory, gastrointestinal, immune, musculoskeletal, neurological and cancer studies. The pig also has been used for interspecies transplantation studies and satisfies the Food and Drug Administration (FDA) evaluation requirements for pharmaceutical drugs. Furthermore, similarities in anatomy and physiology allows anesthetic techniques, drug administration, advanced imaging, ultrasound, endoscopy and surgical procedures to be used in large animal species as they would be in humans. Despite these advantages, several perceived limitations have obstructed their widespread and common use in biomedical studies. These issues include higher costs of maintenance and the need for specialized surgical facilities and veterinary care. Although these limitations have to be considered when developing or using large animal models, the translational data they produce can overcome the issues with rodent models and enable us to make significant advancements to the understanding and treatment of a wide variety of disease conditions.
This special issue welcomes original research papers, review articles and systematic reviews and will focus on:
1. The development and use of innovative translational large animal models to improve pre-clinical research. This can include, but is not limited to:
• Models designed to de-risk the drug discovery pipeline (e.g. dose escalation, toxicology studies, functional measurements)
• Models to collect short and long-term data on therapeutic, pharmacokinetic and adverse effects of novel drugs
• Imaging-based and surgical models
• Therapeutic and diagnostic models
• Genetically altered animals to mimic human disease
• Comparative models to study a variety of human diseases
• Transplantation studies
• Tissue targeted drug delivery models (e.g. eye, CNS, intestine)
2. The advantages and disadvantages of using large animal models. This can include, but is not limited to:
• Comparison of rodent with large animal models
• Practicalities of using large animals
• Alternatives to large animal use in preclinical translational research
• Comparative anatomical, physiological and disease studies between large animals and humans
• Ethical, logistical and practical aspects of their use
• Comparison of large animal variability to that of inbred mouse strains
• Animal welfare considerations, refinement of techniques, determining appropriate animal numbers and the regulation of large animal studies
Pre-clinical research still relies heavily on in vivo rodent models for studying human conditions. These models continue to be popular with scientists as they are considered to be low-cost with the ability to generate reproducible data quickly. Although neoplastic, inflammatory, knockout and transgenic models have provided a wealth of information regarding the pathogenesis of a range of clinical diseases, they unfortunately fail to mimic the entire pathologic characteristics of the human conditions they are trying to model. Rodents are also typically unsuitable for use with advanced imaging techniques (ultrasound, computed tomography, endoscopy) and translational surgical procedures. Because of these issues, there has been increased interest in the development and use of translational large animal models that more closely approximate the clinical and pathologic features of human diseases.
Various large animal species can be used for translational research. Pigs, and perhaps to a lesser extent sheep, have gained significant scientific attention as they share important proteomic, genomic and immunologic similarities to that of humans. Both species have been used successfully for cardiovascular, respiratory, gastrointestinal, immune, musculoskeletal, neurological and cancer studies. The pig also has been used for interspecies transplantation studies and satisfies the Food and Drug Administration (FDA) evaluation requirements for pharmaceutical drugs. Furthermore, similarities in anatomy and physiology allows anesthetic techniques, drug administration, advanced imaging, ultrasound, endoscopy and surgical procedures to be used in large animal species as they would be in humans. Despite these advantages, several perceived limitations have obstructed their widespread and common use in biomedical studies. These issues include higher costs of maintenance and the need for specialized surgical facilities and veterinary care. Although these limitations have to be considered when developing or using large animal models, the translational data they produce can overcome the issues with rodent models and enable us to make significant advancements to the understanding and treatment of a wide variety of disease conditions.
This special issue welcomes original research papers, review articles and systematic reviews and will focus on:
1. The development and use of innovative translational large animal models to improve pre-clinical research. This can include, but is not limited to:
• Models designed to de-risk the drug discovery pipeline (e.g. dose escalation, toxicology studies, functional measurements)
• Models to collect short and long-term data on therapeutic, pharmacokinetic and adverse effects of novel drugs
• Imaging-based and surgical models
• Therapeutic and diagnostic models
• Genetically altered animals to mimic human disease
• Comparative models to study a variety of human diseases
• Transplantation studies
• Tissue targeted drug delivery models (e.g. eye, CNS, intestine)
2. The advantages and disadvantages of using large animal models. This can include, but is not limited to:
• Comparison of rodent with large animal models
• Practicalities of using large animals
• Alternatives to large animal use in preclinical translational research
• Comparative anatomical, physiological and disease studies between large animals and humans
• Ethical, logistical and practical aspects of their use
• Comparison of large animal variability to that of inbred mouse strains
• Animal welfare considerations, refinement of techniques, determining appropriate animal numbers and the regulation of large animal studies
