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

Ribitsch, Iris; Baptista, Pedro M.; Lange-Consiglio, Anna; Melotti, Luca; Patruno, Marco; Jenner, Florien; Schnabl-Feichter, Eva; Dutton, Luke C.; Connolly, David J.; van Steenbeek, Frank G.; Dudhia, Jayesh; Penning, Louis C.


Iris Ribitsch

Pedro M. Baptista

Anna Lange-Consiglio

Luca Melotti

Marco Patruno

Florien Jenner

Eva Schnabl-Feichter

Luke C. Dutton

David J. Connolly

Frank G. van Steenbeek

Jayesh Dudhia

Louis C. Penning


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 in animal models is mutually beneficial for animals, researchers, human and veterinary patients. In this overview we describe advantages and disadvantages of various animal models including domesticated and companion animals used in regenerative medicine and tissue engineering to provide an informed choice of disease-relevant animal models.


Ribitsch, I., Baptista, P. M., Lange-Consiglio, A., Melotti, L., Patruno, M., Jenner, F., …Penning, L. C. (2020). Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do. Frontiers in Bioengineering and Biotechnology, 8,

Journal Article Type Article
Acceptance Date Jul 27, 2020
Publication Date Aug 13, 2020
Deposit Date Aug 13, 2020
Publicly Available Date Aug 13, 2020
Journal Frontiers in Bioengineering and Biotechnology
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 8
Public URL
Publisher URL


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