Miniature Swine for Preclinical Modeling of Complexities of Human Disease for Translational Scientific Discovery and Accelerated Development of Therapies and Medical Devices

Abstract

Noncommunicable diseases, including cardiovascular disease, diabetes, chronic respiratory disease, and cancer, are the leading cause of death in the world. The cost, both monetary and time, of developing therapies to prevent, treat, or manage these diseases has become unsustainable. A contributing factor is inefficient and ineffective preclinical research, in which the animal models utilized do not replicate the complex physiology that influences disease. An ideal preclinical animal model is one that responds similarly to intrinsic and extrinsic influences, providing high translatability and concordance of preclinical findings to humans. The overwhelming genetic, anatomical, physiological, and pathophysiological similarities to humans make miniature swine an ideal model for preclinical studies of human disease. Additionally, recent development of precision gene-editing tools for creation of novel genetic swine models allows the modeling of highly complex pathophysiology and comorbidities. As such, the utilization of swine models in early research allows for the evaluation of novel drug and technology efficacy while encouraging redesign and refinement before committing to clinical testing. This review highlights the appropriateness of the miniature swine for modeling complex physiologic systems, presenting it as a highly translational preclinical platform to validate efficacy and safety of therapies and devices.

Evidence of vasculature and chondrocyte to osteoblast transdifferentiation in craniofacial synovial joints: Implications for osteoarthritis diagnosis and therapy

“…During rodent jaw development, lateral cellular zones of maturation mark the TMJ mandibular condylar cartilage, including the superficial zone (SZ) harboring fibrocartilage stem cells (FCSCs), polymorphic zone (PM) containing heterogeneous proliferating cells, maturation zone (MZ) harboring chondrocytes, hypertrophic zone (HZ) harboring terminally differentiated hypertrophic chondrocytes, and the erosive zone (EZ) where cartilage is resorbed by osteoclasts and osteoprogenitors form bone . While rodent mammals have provided significant insight into mammalian TMJ morphogenesis, large animal models provide significant advantages over rodents, including similarity to human physiology and pathology . Unlike rodent TMJs, pig TMJs are more similar to humans given pig condyles articulate with the articular eminence as opposed to the fossa, have bilateral occlusion, facilitate translational mechanics, have similar disc anatomy, and have analogous biomechanics .…”

“…Therefore, miniature pigs are well‐accepted as an ideal large animal species for studying TMJ . Additional advantages in using miniature pigs as opposed to rodents in modelling human disease are that they grow to a similar size as humans, and have similar organ systems, physiology and metabolism as humans . Relative to rodents, the pig immune response is genetically and functionally analogous to humans making pig an ideal species to model complex human diseases, such as TMJ osteoarthritis, and for predicting human response to joint therapies.…”

“…30,32,33 While rodent mammals have provided significant insight into mammalian TMJ morphogenesis, large animal models provide significant advantages over rodents, including similarity to human physiology and pathology. 34,35 Unlike rodent TMJs, pig TMJs are more similar to humans given pig condyles articulate with the articular eminence as opposed to the fossa, have bilateral occlusion, facilitate translational mechanics, have similar disc anatomy, and have analogous biomechanics. [36][37][38][39][40][41] Therefore, miniature pigs are well-accepted as an ideal preclinical, large animal species for studying TMJ 39 most similar to humans.…”

Comparative Morphometry of the Wisconsin Miniature Swine^TM Thoracic Spine for Modeling Human Spine in Translational Spinal Cord Injury Research

“…by 4-5 months of age and 249-306 kg (550-675 lb.) at full maturity and thus pose challenges in the biomedical research setting [21,22]. In contrast, miniature swine breeds such as the Wisconsin Miniature Swine TM (WMS TM ) developed at the University of WisconsinMadison, range from 25 to 50 kg (55-110 lb.)…”

“…In the context of SCI, the rapidly growing spine and spinal cord of conventional swine do not anatomically and physiologically model the comparatively static nature of the injured spine and spinal cord of a human adult. Additionally, miniature swine more accurately model human vascular anatomy, physiology, and pathophysiology [22], an aspect of biology that is important to the study of SCI. Given these advantages, the WMS is being increasingly considered for SCI studies.…”