Campbell K, Naire S, Kuiper JH. A mathematical model of cartilage regeneration after cell therapy mediated by growth factors. Presented at the 18th Annual Meeting of the Tissue and Cell Engineering Society; July 2018. Newcastle, United Kingdom. Previously presented at the 2016 Internal Conference ‘Recent Trends of Mathematical Research’.

INTRODUCTION: Autologous Chondrocyte Implantation (ACI) is the most commonly used cell-based therapy for treating chondral defects in joints, especially the knee. The procedure involves 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. It has been suggested that co-implanting a mix of the two cell types might improve shortterm cartilage formation1 , but the long-term outcomes are unclear. Our aim is to use a mathematical model of cartilage repair2 to investigate the effects of co-implanting MSCs and chondrocytes on cartilage formation.

METHODS: 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, such as FGF-1 and BMP-2, which are secreted by the cells and thought to influence proliferation and differentiation rates of the cells1 .

Our results indicate the implantation of any MSC and chondrocyte ratio improved the rate of healing within the first year when compared with ACI & mesenchymal stem cell implantation, potentially allowing the patient to become mobile sooner after surgery. The model presented gives us invaluable insight into potentially important advances in cellbased therapies3 .

DISCUSSION & CONCLUSIONS: Our model enabled us to compare cartilage formation following various MSC and chondrocyte implantation ratios (Fig 1). Comparing our 90:10 and 50:50 coimplantation scenarios with our ACI and ASI results from previous work2,3 shows that a mixture of MSCs and chondrocytes delivers the desired effect of increased matrix deposition, as hypothesised1 . Matrix deposition takes place much earlier within the first 12 months of the procedure.

REFERENCES: 1Wu, L., 2013. Mesenchymal stem cells as trophic mediators in cartilage regeneration. Ph.D. thesis. 2Lutianov, M., Naire, S., Roberts, S., Kuiper, J.-H., 2011. A mathematical model of cartilage regeneration after cell therapy. Journal of Theoretical Biology 289, 136–150.3 Campbell, K., Naire, S., Kuiper, J.H., 2017. A mathematical model of cartilage regeneration after cell therapy mediated by growth factors: Part 1 (To be submitted)

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