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

Area of Science:

• Regenerative Medicine and Tissue Engineering
• Translational Science
• Preclinical Research

Background:

• Clinical translation of regenerative medicine technologies faces bottlenecks, particularly in transitioning from small to large animal models.
• Current animal experimental approaches often lack disease relevance, leading to a disconnect between preclinical findings and clinical trial outcomes.

Purpose of the Study:

• To review the advantages and disadvantages of various animal models used in regenerative medicine and tissue engineering.
• To guide informed selection of disease-relevant animal models for preclinical studies.
• To highlight the potential of naturally occurring diseases in large animals.

Main Methods:

• Literature review of animal models in regenerative medicine and tissue engineering.
• Analysis of traditional reductionist versus stepwise approaches (in vitro, ex vivo, in silico, followed by large animals).
• Evaluation of naturally occurring disease models in domesticated and companion animals.

Main Results:

• Small animal models present limitations for predicting human clinical outcomes.
• Large animal models, especially those with naturally occurring diseases, offer greater pathophysiological relevance to human conditions.
• A stepwise approach integrating in vitro, ex vivo, and in silico methods can optimize preclinical screening and reduce in vivo studies.

Conclusions:

• Selecting appropriate, disease-relevant animal models is critical for successful clinical translation in regenerative medicine.
• Naturally occurring large animal diseases represent a valuable, underutilized resource for preclinical research.
• Improved awareness and strategic use of animal models benefit both human and veterinary medicine.