Autologous Chondrocyte Implantation (ACI) is the most commonly used cell-based therapy for treating chondral defects in joints, such as the knee. The procedure begins by inserting chondrocytes, previously expanded in culture, into the defect region. The chondrocytes initiate the healing process by proliferating and depositing extracellular matrix (ECM), which allows them to further migrate in the defect until it is completely filled with new cartilage. Mesenchymal stem cells (MSCs) can be used instead of chondrocytes in this procedure with very similar long term results. The main differences are at early times because MSCs must first differentiate into chondrocytes before cartilage is formed. To enable better understanding of this repair process, we present a mathematical model of cartilage regeneration after cell therapy. The key mechanisms involved in the regeneration process were simulated by modelling cell proliferation, migration and differentiation, nutrient diffusion and ECM synthesis at the defect site, both spatially and temporally. In addition, we modelled the interaction between MSCs and chondrocytes by including growth factors which are produced by these cells and thought to influence each other’s proliferation and differentiation rates. An example is Fibroblast Growth Factor 1, produced by MSCs and stimulating chondrocyte proliferation. Our results show that matrix formation was enhanced at early times under these conditions when compared with simulations not considering the effects of growth factors, reinforcing the importance of cell-to-cell interaction in the healing process. The co-implantation of MSCs and chondrocytes into chondral defects impacted the overall healing time. Our results indicate the implantation of any combination of MSCs and chondrocytes improved the rate of healing within the first year when compared with chondrocyte only or MSC only implantation, potentially allowing the patient to become mobile sooner after surgery. The model presented enables us to better understand articular cartilage regeneration giving us invaluable insight into potentially important advances in cell-based therapies.
