1.Background to research and development
The majority of pharmaceutical products in the 20th century began with low molecular weight compounds, and gradually advanced to biopharmaceutical products, including tissue-derived hormones, proteins and nucleic acids. In the 21st century, major expectations have been placed on regenerative treatment as a basic remedy instead of symptomatic treatment.
To use cultured cells and regenerated tissue as part of medical treatment, the intact cultured cells and tissues must be recovered from culture systems with maintaining their structure and functions. In conventional methods using proteolytic enzymes, damage would occur to cellular membrane proteins, leading to a reduction in both structure and function. By approaching this problem from perspectives in both biomaterials and cell biology, we have been pioneering to the research and development of unique methods for tissue engineering and regenerative medicine. Successful development of temperature responsive culture surfaces, on which dramatic changes in cell adhesion are shown using temperature as a switch, made recovery and implantation of cell sheets possible. The basal surfaces of detached cell sheets are covered with adhesive molecules known as extracellular matrix proteins, deposited during the culture period. This adhesive surface, similar to the glue on ScotchR tape, makes cell sheets grafting to tissue upon the implantation much easier. Layering of cell sheets also became possible to create a three-dimensional tissue structure using a new concept dubbed Cell Sheet Engineering, while also furthering systematic research. This method led to successful new regenerative medical procedures, being applied to cornea, esophagus and heart. Temperature responsive cell culture surfaces are now available on global markets as physical and chemical devices, being used in Europe for the medical treatment of corneas. This type of materials surface design culminated in Cell Sheet Engineering created through the fusion of engineering and medical sciences, and has received high acclaim, both in Japan and around the world.
3.Meaning of the achievements
Employing engineering technology effectively within the field of medical sciences and medical care to create revolutionary new methods of treatment, and spreading this technology around the world, both remain as a major task for Japan as a leading scientific nation. With more than 30 years experience in developing new technologies, we have brought about innovations based on new concepts and methods through the fusion of medical science and engineering together, and were pioneering to deliver regenerative treatment in clinical applications to the world.
A unique system has been created through a multidisciplinary medical and engineering approach, allowing us to achieve a breakthrough in tissue engineering and regenerative medicine for successful use in clinical applications. The successes we have had in developing temperature responsive cell culture surfaces created using nanotechnology, and new regenerative treatment methods for clinical applications from cell sheets created by using thermoresponsive cell culture surfaces, will form the basis for further development in the field of regenerative treatment, to high acclaim both here in Japan and overseas. We are also working towards the commercialization of these techniques.
Reason for the Award
While it has become extremely vital to create revolutionary new fields by merging life and medical sciences with advanced engineering technologies, Teruo Okano, Akihiko Kikuchi and Masayuki Yamato have developed a completely new field called Cell Sheet Engineering that combines the most advanced medical and engineering technologies available. They have subsequently been successful in developing this into the field of regenerative medicine.
Until now, medical care has mostly consisted of drug treatments, yet regenerative medicine using cell biology and tissue engineering is expected to become a major field of growth. The iPS cell technologies developed by Professor Shinya Yamanaka (Kyoto University), the winner of this prize last year, formed the basic cell transformation and conversion technologies that provided major advancements in this field. The Cell Sheet Engineering technology developed by this year’s prize winners takes the results achieved with iPS cell and other technologies at the cell level to higher levels, and is regarded as a unique, practical technology that may ultimately even be used for medical treatment. Tissue engineering, which forms the base for regenerative treatment, had technical limitations as it was difficult to separate cultured cells and tissues from their incubator materials while maintaining cellular and tissue structure intact, however the winners were successful in developing technologies that overcome this barrier. More specifically, based on their experience in polymer synthesis and biomaterials research, the winners focused their attention on temperature responsive polymers that are hydrophobic at 37oC and become hydrophilic at temperatures below 32oC. By processing surfaces of cell culture plates with thermoresponsive polymers, cells were cultivated on thermoresponsive culture surfaces. The technology allowed cells and tissues to be recovered with their structure and functions intact after incubation merely by changing the temperature. This new cell culture technology was used successfully in clinical applications of regenerative medicine for treating incurable diseases in a number of different tissue and organs, including the cornea, heart and esophagus. More specifically, there have been many successful examples where regenerative technology has been used on the cornea, including 30 cases in Japan and 20 in France, and the venture business established by the prize winners is likely to move from clinical trials in Europe to full commercialization of cell sheet products. In clinical trials on dilated cardiomyopathy patients carried out jointly with Osaka University, cell sheets were produced directly from patients who were able to live longer with artificial hearts, and the trial was subsequently successful in the regeneration of heart tissue, allowing these patients to finally move away from using their artificial hearts. The technology is expected to use for the regeneration of periodontal ligament tissue, lungs, livers and other organs into the future.
Accordingly, Teruo Okano, Akihiko Kikuchi and Masayuki Yamato have been selected as prize winners for the Yamazaki-Teiichi Prize for their involvement in the world’s first development of cell sheet engineering in the field of regenerative medical treatment, and the fact that they were able to implement this technology in clinical trials.