Investigation of the Structural Quality of Bone and Cartilage Repair Following Cell Therapy

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Using the body's own cells, known as "cell therapy", is an attractive way to repair worn or damaged body parts. For many years, our Centre has help patients who have knee cartilage damage by using cartilage cells to help repair areas of damaged cartilage. A handful of small studies in humans have shown that stem cells could also be used, not only to help repair cartilage, but also to help repair the underlying bone. The two cells types in combination might help even better. To find out, the charity Arthritis Research UK is funding a clinical trial in our Centre to compare cartilage cells versus stem cells versus the two cell types together. This trial forms a unique opportunity to find out not only which type of cell is better, but also how the cells help repair and which patients are best suited for this treatment. This grant application asks for funding to help us finding out how these different cell types, both alone and in combination, behave inside the joint. We especially like to know how they go on to produce cartilage and bone, arranged in the right way, with the right properties to improve knee function. It will also help us to find out beforehand which cell types are best for which patient, or perhaps identify patients beforehand for whom cell therapy is not a good option. If so, it would save them pinning their hopes on this treatment. Our clinical experience has shown us that the full benefit of cell therapy is seen around one year after cell implantation. At this time point we plan to use a range of techniques to identify and quantify the different types of repair tissue produced. These techniques include Magnetic Resonance Imaging (MRI), visual inspection of the joint itself during knee joint surgery, and examining biopsies of repair tissue down the microscope. MRI can show us how much new cartilage and bone have formed, if the new tissue fills the whole damaged area, how smooth the surface of the cartilage is and how well attached it is to the adjacent normal cartilage. Histology using the microscope and other specialised techniques can show the actual molecules which are present, how they are arranged and how the cells are behaving. We will be able to compare cartilage cells and stem cells and see if one type is better than the other at forming good quality cartilage and/or bone. To identify patients for whom cell therapy is not a good option, we will measure which of the thousands of genes are switched on in the cells that we implant. By comparing between the genes and the measurements we do on the patients at one year, we hope to find gene patterns that identify such patients.