FUJISOFT INCORPORATED (Headquarters: Yokohama City, Kanagawa Prefecture / President: Satoyasu Sakashita) has developed the world’s first technology for maintaining cell survivability and germ-free conditions for regenerated cartilage tissues that have been prepared from ear cartilage for implantation into the nose. This technology allows maintaining the three-dimensional structure of the tissues for an extended period, and is based on a practical development activity for creating an “implant-type regenerated cartilage for congenital facial disorders.” This was one of the developmental subjects from the public participation program for businesses, “Creative Technology-Seeds Development Program/Contract Development*,” offered by the JST.
Preserving regenerated cartilage in its original state for some time after manufacture is necessary because its practical use in medical treatment may sometimes involve, for example, delivery to a hospital some distance away. The recent successful development of such technology will allow FUJISOFT to start preparing for clinical trials with a view to commercialization in the near future. Aiming to complete the clinical trials and regulatory application within 3 years, we are now promoting the application procedures for its commercialization.
This development project was approved on October 10, 2007, by the JST, under which FUJISOFT INCORPORATED, based on a technology transfer from The University of Tokyo, has implemented practical development activities for the creation of an “implant-type regenerated cartilage”—a type of cartilage that is artificially made using a patient’s cells and is used for treating disease- or injury-caused damage of cartilage tissue in the face (nose, etc.) or joints. Traditionally in regenerative medical treatment, cultivated cells are converted into a liquid or gelatinous form and then injected into the damaged part of the joint cartilage, etc.; yet, no product has been developed with both the cubic form and hardness that are essential for advanced regenerative treatment of a distorted nose. However, research carried out in an endowed course of the Department of Cartilage and Bone Regeneration (supported by FUJISOFT) at the Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, has led to the development of the world’s first implant-type regenerated cartilage having the combined features of cubic form and hardness. The first clinical study was initiated in June of this year (Photo 1), and on September 8, 2011, the research team of The University of Tokyo working on the first case announced a favorable clinical course. (The second and third cases are under way.)
In each of the cases of the clinical study, conducted at the Cell Processing Center of The University of Tokyo Hospital, regenerated cartilage was implanted into a patient immediately after being manufactured. However, in view of the future commercialization prospects (considering that future cases might involve deliveries to remote hospitals), it may be necessary, from the viewpoint of product safety, to maintain cell survivability and germ-free conditions for the regenerated cartilage for some time after manufacture. Although the current technology makes it relatively easy to maintain cell survivability in plate culture, it is still very difficult to maintain cell survivability in three-dimensional organ tissues, and this has been a major obstacle to the commercialization of regenerative medical treatment products. For this reason, FUJISOFT INCORPORATED worked on ways to maintain cell survivability and germ-free conditions, in order to keep the three-dimensional tissues in their original state, and has developed a method that allows stabilization of cells in an enclosed container for a long period by enhancing the nutrient exchange efficiency of the cartilage.
Figure 1. Steps for manufacturing regenerated cartilage
- Cartilage cell isolation: Extracting cells from cartilage tissue
- Cell seeding: Putting the isolated cartilage cells into a cell cultivation container to allow them to proliferate
- Passage: Transferring cells from one culture vessel to another
- Cell recovery: Taking the proliferated cartilage cells out of the cell cultivation container
- Cell administration: Mixing the cultivated cells with atelocollagen and administering the mixture into the scaffold material
- Gelation: Solidifying the product (into three-dimensional structures)
The regenerated cartilage manufactured using the method developed by FUJISOFT INCORPORATED has already been tested in mice (at The University of Tokyo), showing favorable cartilage formation after implantation (Photo 2). The results also showed that the cartilage had almost the same capability as the regenerated cartilage made using the method adopted in the clinical studies at The University of Tokyo. FUJISOFT INCORPORATED intends to initiate preparatory activities for clinical trials with a view to the commercialization of this product. Aiming to complete the clinical trials and regulatory application within 3 years, we are now promoting the application procedures for its commercialization.
Moreover, by means of systematizing the manufacturing process with autologous cells through use of proprietary technologies of IT companies (as used in the clinical research at The University of Tokyo), we were able to obtain favorable results. It also allowed us to prevent contamination (e.g., permeation of hazardous substances), standardize the process, and maintain product uniformity. All records from the manufacturing process have been converted into data sets, and we intend to develop methods for manufacturing regenerated cartilage tissues that can be used safely, as well as methods that would make it possible to standardize product quality through systematization of the manufacturing process (Photo 3).
FUJISOFT INCORPORATED aims to realize commercialization by FY 2015 and plans to manufacture the products at the Cell Processing Center in our office in Kinshicho. We hope to attain sales of 4 billion yen in the first 5 years of commercialization.
Photo 1. Regenerated cartilage
Photo 2. TB-dyed image after implantation
Toluidine blue (TB) dyeing: A dyeing method that gives the cartilage tissue a red-violet color
Photo 3. A clean bench for the system (left), a pipette (center), and an RFID-tagged petri dish (right)
Patient information is traced by reading a radiofrequency identification (RFID)-tagged petri dish, using an RFID tag reader with a built-in clean bench for the system. Additionally, this system can help prevent contamination and help manufacture uniform products by manipulating the use of the pipette in the system that manages the manufacturing process.
* Creative Technology-Seeds Development Program/Contract Development
The Creative Technology-Seeds Development Program/Contract Development commissions the development of research results from universities and public research institutes that have a particularly high risk of development by companies by bearing research expenses and pursuing commercialization. This program has been reorganized into the “Promotion System for High Technology Development (Adaptable and Seamless Technology Transfer Program through Target-driven R&D [A-STEP])” in a progressive manner.
Regenerative Medical Treatment Research Division, FUJISOFT INCORPORATED
2-19-7 Kotobashi, Sumida-ku, Tokyo, 130-0022 JAPAN
Tel: +81-3-6844-0801, Fax: +81-3-6844-0802
Takanori Hirao, Yukio Kenmochi
Department of Industry-Academic Alliance, Innovation Headquarters, Japan Science and Technology Agency
5-3 Yonbancho, Chiyoda-ku, Tokyo, 102-8666 JAPAN
Tel: +81-3-5214-8995, Fax: +81-3-5214-0017
Tomiko Uemura, Chiaki Nishino
Corporate Communication Department, Corporate Planning Group, FUJISOFT INCORPORATED
3 Kanda-Neribeicho, Chiyoda-ku, Tokyo, 101-0022 JAPAN
Tel: +81-3-5209-5910, Fax: +81-3-5209-6085
Department of Public Relations and Science Portal, Japan Science and Technology Agency
5-3 Yonbancho, Chiyoda-ku, Tokyo, 102-8666 JAPAN
Tel: +81-3-5214-8404, Fax: +81-3-5214-8432