Research and Development of Human Cellular and Tissue Engineering for Clinical Development/CRDS-FY2010-SP-03
Executive Summary

The strategic initiative entitled "Research and Development of Human Cellular and Tissue Engineering for Clinical Development" provides the research and development strategy to apply recent technological achievement of cell dynamics biology to regenerative medicine, transplantation immunology, and artificial organ technology, which would progress the innovative tissue and biomaterial engineering to reconstruct multi-cellular structure(s) for specific vital function of human organ(s) ready to implant in human bodies.

The research and development plan suggested in this proposal would deliver safer and high-functioning artificial organ(s)/tissue(s) to patients who have no alternative treatment. It would also expand treatment opportunity using organ/tissue implants, resulting in reducing medical care costs on the patients currently depending on symptomatic therapy, and also solving ethical and technological (including immunology) problems of organ donation between humans. Thus, promoting this research and development strategy would improve health progress the industrialization of life science technologies, and resolve the global pending issues of ethical, legal, social implications of organ transplant businesses.

Currently, various regulations and limitations associated with organ donation/ transplantation in Japan cause mismatch between the numbers of patients and donors of organ transplants, resulting in the shortage of organs for implantation. In addition, the number of patients who visit developing countries from developed ones for organ transplantation is increasing, which causes among poverty societies illegal organ trades or abduction and murder of children to retain organ supply for transplantation. Considering such situation, the sixty-third World Health Assembly of World Health Organization (WHO) adopted WHA63.22 on 21 May 2010, recommending each member country to develop a system for the altruistic voluntary non-remunerated donation of cells, tissues and organs in accordance with nation capacities and legislation1. This adoption suggests that each nation should make considerable effort to provide sufficient organ supply for transplantation within its own country. Because social need for the organ supply is quite urgent, technologies to make up artificial cells, tissues, and organs would be anticipated internationally.

In this proposal, we recommend the following three research and development projects to progress technological basis and elements of three-dimensional tissue engineering followed by the clinical development and industrialization.

Development of cell and tissue engineering technology to reconstruct an organ or develop multi-cellular structures which retain vital function of the given organ
Development of manufacturing process of an established artificial organs and multi-cellular structures
Establishing immunological approaches to improve graft survival rate including development of useful indicators and measurement technology

The goal of the first project is to establish innovative technological basis manipulating various cells and biomaterials for making artificial organs and multicellular structures. The second project aims the establishment of well-qualified manufacturing process applicable to mass and stable production. The last one aims molecular-level immunological control system, in terms of immunological tolerance and development of indicators which measure the manufacturing processes, as well as a simulation system for the patient's vital condition.

Regarding the research team structure for these projects, it is required that each researcher (or research team) in the team set his/her goal and share his/her achievements across members. And it is recommended that both academic and clinical institutes are involved in the projects and integrate elemental technology for clinical science-oriented, goal-oriented research and development. Further, to facilitate clinical development which connects clinical science achievements to social benefits, it is important to keep close contact with both industries and competent authorities throughout the projects.

In this initiative, 10 years are estimated to establish an initial manufacturing process of multi-cellular structure with specific vital function(s), and biological/medical progress for successful engraftment of the implanted artificial structures, which includes pre-clinical trial. Additional 5 years may be required to establish an efficient manufacturing process as well as to pass clinical trials, so that the estimated achievement period is at least 15 years.