Perspectives on Animal Models Utilized for the Research and Development of Regenerative Therapies for Articular Cartilage

Abstract

Animal models are integral and indispensable for biomedical research and regenerative medicine studies, as these provide invaluable information for systemically evaluating the potential risks and efficacy of newly developed biomaterials, drugs, medical devices, and therapeutic modalities, prior to initiation of human clinical trials. Nevertheless, it is important to be aware of the unique strengths and limitations of the various different small and large animal models commonly utilized for biomedical research as well as the various challenges faced in extrapolating results acquired from animal studies and the risks of data misinterpretation. This review will thus critically examine various animal models utilized for studies on articular cartilage regeneration. Particular emphasis will be placed on comparing and analyzing the unique strengths and limitations of each animal model, with the aim of establishing principles for evaluating the suitability of different animal models for individual studies as well as for comprehensive interpretation and extrapolation of results obtained from various animal species. Additionally, this review will also discuss to evaluate animal studies with in situ imaging techniques, how the animal genome may result in variability in experimental outcomes, as well as the contribution of animal models to the development of cartilage tissue engineering.

Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes

“…Previous studies comparing human and mouse development in kidney 13 , liver 14 , lung 15 and blood 16 have all noted significant transcriptional and regulatory variance between the two species, coupled with high levels of conservation in tissue-specific gene networks. Given the significant disparities in growth plate development 17 , 18 , tissue thickness 19 , 20 , mechanical forces 21 and potential for regeneration 22 , 23 between mice and humans, we reasoned that a more comprehensive understanding of the underlying gene expression signatures that drive specification, diversification and function of musculoskeletal tissues during human ontogeny would provide insight into the molecular mechanisms of human development required for important therapeutic advances.…”

Enhancement of the chondrogenic differentiation of mesenchymal stem cells and cartilage repair by ghrelin

“…However, the rat osteochondral defect model has its limitation and do not completely reflect cartilage lesions in the human clinical model. The joints of rats have stronger capacity to heal spontaneously, when compared to the human model . The defect created in rats is osteochondral which result in marrow infiltration, while human cartilage lesions pre‐dominantly have their osteochondral bone intact.…”

“…The defect created in rats is osteochondral which result in marrow infiltration, while human cartilage lesions pre‐dominantly have their osteochondral bone intact. Additionally, the rat knee differs anatomically to that of human knee, with different mechanical loading to the joint. Both these inherent factors are known to affect cartilage repair, and might affect the in vivo effects of TGF‐β and ghrelin on cartilage regeneration.…”

Articular Repair/Regeneration in Healthy and Inflammatory Conditions: From Advanced In Vitro to In Vivo Models

“…Animal models are widely used to study cartilage response to injury and test new repair/regeneration strategies ( Table 2 ), and their strengths and limitations to answer a particular question should be carefully considered. [ 72 ] The most employed methodology for in vivo models of cartilage repair is the creation of surgical focal defects in the knee's cartilage. [ 73 ] However, all small or larger animal models have advantages and limitations that need to be critically evaluated, making the best choice based on the research question being addressed.…”

“…[ 73 ] However, all small or larger animal models have advantages and limitations that need to be critically evaluated, making the best choice based on the research question being addressed. [ 72,74 ] In the case of cartilage repair research three main important factors need to be considered: the size of the joint, the cartilage thickness, and intrinsic healing ability of that cartilage…”