Osteoarthritis (OA) is a joint disease, caused by breakdown of the cartilage in the joint — cartilage is a ‘biological lubricant’ that contains no blood vessels or nerves, but mainly cells known as chondrocytes. Typical symptoms are joint pain and stiffness. Often, the symptoms develop over several years, and significantly affect daily life as it typically reduces a patient’s mobility. OA leads to the gradual loss of a human’s mobility, thus negatively affecting a patient’s quality of life. Osteoarthritis is one of the most prevalent joint diseases in mature women. Structural changes include loss of articular cartilage, subchondral bone sclerosis, and formation of cysts and osteophytes. The low cellularity and vessel-less nature of articular cartilage means that its capacity to self-regenerate after injury or degeneration is limited. Mild OA is treated conservatively with administration of anti-inflammatory (NSAIDs) drugs, intra-articular injection of corticosteroid and/or hyaluronic acid and controlled exercise. However, surgical treatment may be required as the disease progresses, while no cure exists for stopping its progression. The main treatments are high tibial osteotomy and total knee replacement.

Various arthritis models, such as surgical intervention and intra-articular drug injection, have been used to study cartilage regeneration. The anterior cruciate ligament resection model is the surgical intervention model used most frequently. In this model, anterior cruciate ligament resection triggers cartilage degeneration, subchondral bone sclerosis, and osteophyte formation, which mimic the pathological changes observed in human OA.  Chondrocyte implantation products are sometimes applied, but for OA of the knee, such implantation approaches are not effective. Now, professor Masato Sato at the Tokai University School of Medicine, and colleagues have shown that an approach combining conventional surgery and chondrocyte cell-sheet transplantation is a promising therapy for OA of the knee. The researchers had shown earlier that transplantation of chondrocyte sheets in animal models promoted cartilage repair, but such transplantations had never been applied to humans. Dr. Sato and colleagues first performed conventional surgery and then chondrocyte sheet-cell transplantation on eight patients with OA of the knee.

The transplantations were autologous, meaning that material from the individual was used. This is both disadvantageous (healthy cartilage from another, albeit limited, area in the knee has to be sacrificed) and advantageous (no foreign material enters the body). Because of the need for autologous material, it is unrealistic to perform the procedure more than two times on one and the same patient. The result of the combined approach was assessed by various techniques, including X-ray imaging (before and after the procedure), magnetic-resonance imaging, arthroscopy and photoacoustic measurements of cartilage viscoelasticity. Scientists point out a few limitations of their study. Only eight patients were treated, and although promising outcomes were recorded over the course of a 3-year observation period, longer-term observations are needed to fully assess the proposed combined therapy. Therefore, it is more like a pilot study. Because the therapy is a combination of different procedures, it is challenging to make it compliant with regulations — usually requiring clear evidence of the effect of every single intervention.

Quoting the researchers who worked on the Japan Agency for Medical Research and Development (AMED) grant program: “Although the method used in our clinical study is challenging for the regulatory authorities, we believe it is essential to continue investigating the outcomes in more patients with OA of the knee. Determining the true effectiveness of this therapy for OAK requires longer-term follow-up and strict comparative studies”. Following the favorable results of the clinical trials, the treatment developed by Sato and his group was approved by Japan’s Ministry of Health, Labor and Welfare as an advanced medical treatment for osteoarthritis of the knee.

• Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry

Scientific references

Ringe J, Hemmati-Sadeghi S et al. J Orthop Res. 2019 Apr 12. 

Takatori N et al., Watanabe M. Regen Ther. 2018 Aug 24; 9:24-31. 

Sato M, Uchida K et al. Arthritis Res Ther. 2012 Feb 7;14(1):R31.