At the meeting of the MHLW panel on medical equipment and IVD (in vitro diagnostics) held on 23 August 2007, the application for cultured skin tissue manufacture and sales by the Aichi Prefecture venture company Japan Tissue Engineering (J-TEC) was approved. This is the first time that something produced from a part of a human body has been approved in Japan for regenerative medicine purposes. The product will be able to be marketed once the approval of the pharmaceutical affairs panel of the Pharmaceutical Affairs and Food Sanitation Council has been given. Cultured skin tissue is made by sampling skin tissue from an area of uninjured skin from a patient with severe skin lesions or burns, culturing this with mouse cells in cow embryo blood plasma to produce transplantable sheets. It is said to be possible to manufacture 10 sheets sized 8 cm by 10 cm in about three weeks. These can then be transplanted to the problem areas on the patient. J-Tec undertakes everything from transport to culturing and testing, and the current skin tissue sales price is 10 million yen (approx. US$87,000). This approval is attracting attention as showing that regenerative medicine has at last reached the commercialization stage in Japan, but at the same time it is also evidence of the steadily advancing resourcification and commercialization of the human body. (Asahi Shinbun 2007/08/24)
The MLHW review committee on clinical research on human stem cells met on 29 August 2007 and approved four projects applied for by Osaka University, the National Cardiovascular Center and Kyoto University (two projects). The diseases under study are: Osaka University, ischemic heart disease (IHD); National Cardiovascular Center, cardiogenic brain embolism; and Kyoto University, intractable osteopathy. These are the first approvals since the guidelines for clinical research on human stem cells were enforced on 1 September 2006. (Biotechnology Japan 2007/08/30)
The US Food and Drug Administration (FDA) announced on 26 July 2007 that a patient had died from side-effects after administration of an experimental drug during gene therapy for arthritis being conducted by the venture corporation Targeted Genetics Corp. (Seattle), and that therefore the clinical trials had been suspended. (Mainichi Shinbun 28 July 2007) (See BJ September 2007
The vector (gene carrier) used was the adeno-associated virus (AAV). It is inevitable that this side-effect incident will have a very serious effect on gene therapy as a whole since the AAV is considered to be relatively safe compared to other viruses. Up to now, it has been pointed out that gene therapy has many problems with safety, and has been criticized as being experiments on human guinea pigs for the sake of vector development. There have been cases of patients contracting leukaemia as a side-effect in France and cases of death in the United States from the use of retroviruses and adenoviruses in gene therapy. From the point of view of effectiveness also, despite the fact that it is now 10 years since the first project began in Japan, no case of full recovery from an illness has been reported, and in many cases the gene therapy has been used in combination with conventional treatment, making the effectiveness of the gene therapy unclear.
Gene therapy has thus run into a road block, but the possibilities for the application of the technology is increasing from another angle. A research group under Professor YAMANAKA Shinya at the Kyoto University Institute for Frontier Medical Sciences published a paper in the 11 August 2006 electronic edition of the science journal "Cell" claiming that they had produced cells analogous to ES cells (embryonic stem cells), known as induced pluripotent stem cells, or iPS cells, from cells from the skin of adult GM mice. (See BJ July
and August 2007
)This iPS cell was produced from the skin cells of mouse by the introduction of four factors of a specific RNA, the RNA factors being introduced by the use of a retrovirus as the vector. Although the efficacy of gene therapy is not becoming apparent, the technology developed by gene therapy to insert external genes is finding uses in previously unpredictable areas. It is said that Prof. Yamanaka and his group are now researching with the aim to produce human iPS cells.
The current top-runner for biotechnology that is attracting attention is regenerative medicine, the main method for which is gene therapy. Cells which have aged or have become damaged through illness will be replaced by new cells, thereby regaining the normal functioning of the body. However, the new cells need to be altered in various ways, and the tool for this processing will be external gene insertion, in other words gene recombination (genetic engineering or modification). Thus far, among the research projects using human ES cells that MEXT has approved, there are already four projects which include gene recombination. (See BJ September 2007
) It is now expected that the introduction of foreign genes into human ES cells for the purposes of raising the efficiency of differentiation or for immunosuppression will become more and more active in the near future.