Research Content

Research objectives (background)

Musculoskeletal disorders such as osteoarthritis of the knee (OA) not only decrease activity of daily living (ADL) but also negatively impact quality of life (QOL). OA is an intractable degenerative disease of the joint that is slow progressing and widely prevalent. To date, no fundamental treatment exists, and with a global aging population, the increasing number of OA patients is a serious concern, making a fundamental treatment for OA imperative.
Regenerative medicine for articular cartilage has been implemented domestically on one hand, but current treatments fail to address cartilage defects associated with degenerative diseases such as OA. Our research focuses on treating such difficult to treat cartilage defects with the regeneration of hyaline cartilage, which better supports the mechanistic function of normal joints.

Prior to clinical studies

We have conducted basic research under the concept that as long as the surface layer of articular cartilage is regenerated properly, the underlying and deep layers can self-regenerate through intrinsic regenerative functions. “Cell sheet” technology developed by Professor Teruo Okano at the Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s University, allows the collection of cells and surrounding extracellular matrix from the culture dish, noninvasively and without enzymatic treatment, in the form of a thin sheet, using a specially coated temperature-responsive culture dish. We have confirmed the efficacy of chondrocyte sheets fabricated on such temperature-responsive culture dishes in various animal experiments, and specifically, the treatment effects of such sheets on both partial-thickness defects (those that do not reach the subchondral bone) and full-thickness defects (those that reach the subchondral bone) are worth special mention in terms of their uniqueness in regenerative medicine.
However, in order to make this treatment available clinically, rigorous safety evaluations were necessary. We had hoped to make this treatment available rapidly, but more than three years were spent to meet regulatory guidelines of the Ministry of Health, Labour and Welfare of Japan, and finally in 2011, we began a clinical study for the transplantation of chondrocyte sheets fabricated from the patients’ own cells (transplantation of autologous chondrocyte sheets). We confirmed the safety of this treatment method and improvement in clinical scores and verified the regeneration of hyaline cartilage in all eight patients entered into the study.

Future prospects

All patients in the clinical study for the transplantation of autologous chondrocyte sheets have reported favorable progress in their recovery at three years post-surgery, and we are in preparations to apply for Advanced Medical Care. At the same time, to further expand the clinical prospects of chondrocyte sheets and to transfer the technology to industry, we are conducting a second clinical study for the transplantation of chondrocyte sheets fabricated from other donor cells (transplantation of allogeneic chondrocyte sheets), and as of fall of 2017, 2 patients have been treated through this method and are recovering favorably.
Our focus now is to further determine the potential of chondrocyte sheets for the treatment of cartilage defects associated with OA through the clinical trial and to make this treatment available clinically. Furthermore, we work in hopes that our daily research lead to a fundamental and overall treatment for OA, so as to contribute to the increase in patient ADL and QOL through the preservation of one’s own joints.

Organizational structure for collaborative research

【List of associated members】

Internal departments
Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine
Department of Clinical Pharmacology, Basic Medical Science, Tokai University School of Medicine
Department of Regenerative Medicine, Basic Medical Science, Tokai University School of Medicine
Department of Orthopaedic Surgery, Tokai University Hospital
Cell Processing Center, Tokai University Hospital
General Clinical Research Center (GCRC), Tokai University School of Medicine
Research collaborators
Hidenori Akutsu: Center of Regenerative Medicine, National Center for Child Health and Development
Reiko Kato: Division of Medical Devices, National Institute of Health Sciences
Hiroshi Nagashima: Department of Life Science, School of Agriculture, Meiji University
Institution partners for research collaboration
Department of Medical Engineering, National Defense Medical College
Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University
Industrial partners for research collaboration
CellSeed Inc.
DNA Chip Research Inc.

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Our reseach was introduced on a news program in Taiwan

Our research was introduced on NHK World TV