Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

Abstract

Rapid developments in Regenerative Medicine and Tissue Engineering has witnessed an increasing drive toward clinical translation of breakthrough technologies. However, the progression of promising preclinical data to achieve successful clinical market authorisation remains a bottleneck. One hurdle for progress to the clinic is the transition from small animal research to advanced preclinical studies in large animals to test safety and efficacy of products. Notwithstanding this, to draw meaningful and reliable conclusions from animal experiments it is critical that the species and disease model of choice is relevant to answer the research question as well as the clinical problem. Selecting the most appropriate animal model requires in-depth knowledge of specific species and breeds to ascertain the adequacy of the model and outcome measures that closely mirror the clinical situation. Traditional reductionist approaches in animal experiments, which often do not sufficiently reflect the studied disease, are still the norm and can result in a disconnect in outcomes observed between animal studies and clinical trials. To address these concerns a reconsideration in approach will be required. This should include a stepwise approach using in vitro and ex vivo experiments as well as in silico modeling to minimize the need for in vivo studies for screening and early development studies, followed by large animal models which more closely resemble human disease. Naturally occurring, or spontaneous diseases in large animals remain a largely untapped resource, and given the similarities in pathophysiology to humans they not only allow for studying new treatment strategies but also disease etiology and prevention. Naturally occurring disease models, particularly for longer lived large animal species, allow for studying disorders at an age when the disease is most prevalent. As these diseases are usually also a concern in the chosen veterinary species they would be beneficiaries of newly developed therapies. Improved awareness of the progress

Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation

“…This trend has been particularly important for structural repair and functional restoration of tendons [ 1 , 2 , 3 , 4 ]. Increasing interest around regenerative medicine has prompted widespread efforts toward preclinical and clinical research to eventually provide physicians and patients with effective management strategies for debilitating wounds or tissue defects [ 5 , 6 , 7 ]. Therein, additive or synergistic combinations of surgical intervention and cell-based therapies may prove to be essential for optimization of clinical outcomes.…”

Serial Ultrasonographic and Real-Time Elastosonographic Assessment of the Ovine Common Calcaneal Tendon, after an Experimentally Induced Tendinopathy

“…In the last twenty years, considering its low cost, availability and its acceptance by the society as research animal, the ovine specie has become one of the most commonly used large animal model in orthopedic research [ 26 ]. The results of these researches have often been the starting point for the diagnosis and treatment of pathologies in humans and many other animal species.…”

Small Ruminants and Its Use in Regenerative Medicine: Recent Works and Future Perspectives

“…The equivalence of age between humans and sheep is also well defined, allowing this variable to be used in the translation of results between the two species [ 25 ]. Surgery and anesthesia equipment are similar in size and characteristics to those used in human medicine, not creating spatial and budgetary limitations as with other large models (e.g., cattle) [ 26 ]. The similarities between human and sheep lung structure and functions, namely in terms of respiratory rate, resistance, and air flow, make the sheep a good model for asthma studies [ 27 ] and also for other complex diseases with genetic origin such as cystic fibrosis [ 28 ].…”