Mesenchymal Stem Cells in a Clinical Trial to Heal Articular Cartilage Defects

Musculoskeletal diseases are growing in the Norwegian population and are currently the largest group of the chronic diseases (31%). Musculoskeletal diseases are the largest cause of disability on the working part of our population (49%). The most frequent problems are rheumatism, osteoarthritis and unspecific back pain. The most common known etiology is traumatic events towards the joint. Often, the degenerative development starts with a small injury to the cartilage on weightbearing surface of the joint. This leads to changes in the surrounding cartilage, indicative of degenerative joint disease or arthrosis. When the injured area becomes larger than 2 cm2, the patients seem to experience pain. Our group has shown that 11% of patients, who underwent an arthroscopy for knee pain, had a cartilage injury on weightbearing surface with depth down to bone (grade IV) (Aroen et al.).Unfortunately, articular cartilage shows a very limited capacity of healing. Several surgical techniques have been developed to fill the cartilage defects, but so far none of them have been able to produce normal cartilage Chondrocyte implantation techniques are at date the most popular treatment, but have not demonstrated their superiority to other cartilage repair techniques. Some clinical randomised studies exist though a more thorough review of the cartilage repair methods in a study by Jakobsen and coauthors verified that no conclusion could be made considering treatment options for articular cartilage injury (Jakobsen, Engebretsen, and Slauterbeck). Although the natural history of these lesions is not finally outlined it is clear that for some patients the disruption of the cartilage surface imposes disability especially for the young athlete. The clinical studies report a significant improvement from the preoperative status although full knee function is not obtained with either of the techniques available today (Bentley et al.;Brittberg et al.;Horas et al.;Knutsen et al.). The expected Lysholm score of 80 and the standard deviation tends to be large or is not reported which illustrating the considerable variation and that full knee function is not obtained (Peterson et al.).The impact of disrupting the cartilage surface to obtain chondrocytes for culturing has not gained much attention in the clinical studies using this repair method. However it is reported that adverse effects exist as a result of this harvesting of chondrocytes for culturing (Whittaker et al.). Whittaker and coauthors observed that the harvesting of chondrocytes for cell culturing and subsequent implantation in talus resulted in a mean 15 points reduction in Lysholm score in 7 out of 10 patients. Furthermore, additional even in the best hands a mean Lysholm score of 79 are obtained for a single lesion at the femoral condyle (Peterson et al.). Even though the new scaffolds seem to reduce the rate of reoperation as a result of graft hypertrophy from 21 % to 9 %, the harvesting procedure of cartilage may still contribute to the suboptimal by this approach (Bartlett et al.;Gooding et al.). Consequently, there is a need for a better causing less morbidity when harvesting. Mesenchymal stem cells (MSC) represent an alternative cell source with the potential of generating hyaline cartilage without the same adverse effects. In addition with MSC more cells will be available for culturing with the potential of treatment of larger lesions possible. Furthermore, the repair potential of mesenchymal stem cells is not expected to decrease with age indicating that also the aging athlete may benefit from a procedure based on cartilage repair with this cell source (Dressler, Butler, and Boivin). The use of mesenchymal stem cell aspirate from the iliaca crest under a periosteum flap support the view that this might be an option to treat knee cartilage defects with success, although this study also has periosteum hypertrophy as a side effect in one of the patients (Slynarski, Deszczynski, and Karpinski). The beneficial effects of this therapy has also been reported in other studies both clinical and experimental ones (Takagi et al.;Wakitani et al.;Wakitani et al.;Wakitani et al.). Thus, the current project will investigate if the similar results can be obtained with mesenchymal stem cells as with chondrocytes both delivered in a commercial available scaffold in clinical trial with patients eligible for the current treatment options.