Mass production technology for cartilage cell sheets established — A path toward "joint-preserving treatment" for knee osteoarthritis

In order to treat a large number of knee osteoarthritis patients, Professor Masato Sato of the Department of Orthopaedic Surgery at Tokai University Hospital, with the cooperation of Hitachi, Ltd. and Hitachi High-Tech Corporation, has established a technology for the mass and stable production of allogeneic cartilage cell (chondrocyte) sheets. In a clinical trial that began in June 2025, transplant surgery was performed on four knee osteoarthritis patients between the ages of 50 and 60.

As of February 2026, no serious adverse events have been observed, and the clinical trial is ongoing. If a next-generation allogeneic cartilage cell sheet manufacturing system based on automated culture is established, the likelihood of being able to stably supply cell sheets of uniform quality will increase. It is hoped that this will expand the new treatment option of "joint-preserving therapy" for knee osteoarthritis. The findings were presented at the Japanese Society for Regenerative Medicine.

Knee osteoarthritis is a representative musculoskeletal disease that increases with age. The estimated number of patients in Japan is approximately 25.3 million, of whom approximately 8 million are estimated to have symptoms such as pain.

Once damaged, articular cartilage is difficult to repair naturally, and current treatment is centered primarily on conservative therapy aimed at reducing pain and improving function. When the condition progresses, surgical treatment such as total joint replacement becomes necessary.

Sato and his colleagues therefore developed an autologous cartilage cell sheet. By transplanting this sheet directly onto the cartilage defect, it adheres to the affected area and promotes protection of the defect and repair of the cartilage. This research is currently being conducted as Advanced Medical Care B under the Ministry of Health, Labour and Welfare.

However, autologous cartilage cell sheets present certain challenges. Surgery is required to collect the cells, the quality of cells may vary from patient to patient, and the quantity of cell sheets that can be provided at one time is limited.

From 2017, clinical research has been conducted using allogeneic cartilage cell sheets utilizing cartilage tissue that would otherwise be discarded during polydactyly surgery. Because cartilage cells derived from polydactyly are immature, they have high proliferative capacity and have shown advantages in building a stable and efficient supply system, including shortening the sheet preparation period by seven days.

In the clinical research, safety and efficacy were evaluated in 10 knee osteoarthritis patients, and favorable outcomes were confirmed from both perspectives. A company-led Phase III trial began in 2025, and development toward practical application is steadily progressing. Because knee osteoarthritis affects such a large number of patients, mass production and standardization of quality are indispensable for the widespread adoption of cartilage cell sheets.

Conventional allogeneic cartilage cell sheets required processes using temperature-responsive culture dishes and manual work by skilled cell culture technicians, presenting challenges in terms of production efficiency, cost, and the risk of mix-ups.

The next-generation allogeneic cartilage cell sheet involves a revised process adapted for production using the iACE automated cell culture device, a closed-system apparatus.

In non-clinical studies conducted in 2023 and 2024, next-generation allogeneic cartilage cell sheets were transplanted into cartilage defect models in immunodeficient animals. It was confirmed in the studies that next-generation allogeneic cartilage cell sheets produced using the iACE showed cartilage repair capacity equivalent to that of the conventional method.

Because the device can produce approximately 640 sheets in a single culture run, this theoretically corresponds to enough sheets for approximately 50 patients, based on the established usage of approximately 10 to 15 sheets per case.

In the next-generation allogeneic cartilage cell sheet transplantation trial, since last June, four patients have each received 10 to 15 next-generation allogeneic cartilage cell sheets produced using the iACE, sheets that passed in-process safety testing and specification testing, in combination with high tibial osteotomy (HTO). Follow-up evaluation is currently ongoing.

Sato commented: "Once damaged, articular cartilage is difficult to repair naturally, and the options for biologically regenerating cartilage in knee osteoarthritis have been limited. We have been advancing research on autologous cartilage cell sheets since 2004, and have been conducting this work as Advanced Medical Care B. However, we faced challenges including the need for surgery to collect cells and constraints on the quality and number of sheets that could be produced for each patient. We therefore expanded our approach to allogeneic cartilage cell sheets using immature cartilage cells that would otherwise be discarded during polydactyly surgery and have now further advanced this to a next-generation allogeneic cartilage cell sheet that can be produced uniformly and in large quantities through automated culture technology. Improving uniformity and traceability are also important goals. In the future, we hope to broaden the regenerative medicine options for joint preservation and develop this into a treatment that can be reliably delivered to more patients."