Sheep as a model for evaluating mesenchymal stem/stromal cell (MSC)-based chondral defect repair

Abstract

Osteoarthritis results from the degradation of articular cartilage and is one of the leading global causes of pain and immobility. Cartilage has a limited capacity for self-repair. While repair can be enhanced through surgical intervention, current methods often generate inferior fibrocartilage and repair is transient. The development of tissue engineering strategies to improve repair outcomes is an active area of research. While small animal models such as rodents and rabbits are often used in early pre-clinical work, larger animals that better recapitulate the anatomy and loading of the human joint are required for late-stage preclinical evaluation. Because of their physiological similarities to humans, and low cost relative to other large animals, sheep are routinely used in orthopedic research, including cartilage repair studies. In recent years, there has been considerable research investment into the development of cartilage repair strategies that utilize mesenchymal stem/stromal cells (MSC). In contrast to autologous chondrocytes derived from biopsies of articular cartilage, MSC offer some benefits including greater expansion capacity and elimination of the risk of morbidity at the cartilage biopsy site. The disadvantages of MSC are related to the challenges of inducing and maintaining a stable chondrocyte-like cell population capable of generating hyaline cartilage. Ovine MSC (oMSC) biology and their utility in sheep cartilage repair models have not been reviewed. Herein, we review the biological properties of MSC derived from sheep tissues, and the use of these cells to study articular cartilage repair in this large animal model.