Japanese ethical guidelines for human genome/gene analysis research were revised　on February, 2013. This amendment was focused on corresponding devastating progress of　methodology of gene analysis and the changes in way and concept of genome research. I participated in the review committee of the amendment as a president of Council for Protection of Individual Genetic Information. Here, I mention the outline of the revision with personal comments.

View full abstract

The ethical guidelines on human genome research was revised in 2013 and we are now on a new stage in the regulation. Because of innovative scientific and technological developments, the number of new issues to be discussed is increasing even after the establishment of the revised guidelines. At least we need broad temporary agreements on the yet unsolved issues. As I　mentioned in this article, the most important thing is the establishment of platforms to discuss the arising problems on rapid progress of genome research from diversified standpoints such as technical advancement, social atmosphere, and trends on the use of human genome information in research and medical practices. In this article, I covered the issues on whole genome analysis of HeLa cells and discussed what and how the 'consent' should be, especially focusing on broad consent. These problems remain to be a central issue in the use of human materials and information in science research.

View full abstract

The tri-ministrial guideline on human genetic/genomic research (Ethics guidelines for human genome/genetic analysis research) was revised in 2013. In this paper, the main points of the changes are summarized. This guideline was originally drafted more than 10 years ago, amid peopleʼs wariness of human genetic analysis. Rationalization of the guideline, in response to the past and possible evolution of research methodologies, had been expected. Furthermore, increased disparities between the guideline and other national ethical guidelines were also points of discussion. Although these problems remain unresolved even after the amendment work, there are some points of amendments to be noted. Especially, enlarged responsibilities of researchers and research institutes concerning treatment of genetic information/data warrant attention.

View full abstract

Liver has key roles in physiologically important metabolism such as gluconeogenesis, detoxification, synthesis of plasma proteins, etc. Liver transplantation is an effective treatment for end stage liver diseases although there is a serious problem of donor shortage. In addition, human, not animal livers are an invaluable source of hepatocytes for drug development because there is a significant species difference in drug metabolism. In recent years, the stem cell derived functional hepatocytes attract attention in the field of both regenerative medicine and drug metabolism and pharmacokinetics (DMPK). Because of the abilities of infinite replication and pluripotent differentiation, ES and iPS cells are hoped as another source of hepatocytes. Namely, the functional hepatocytes will be a useful tool for cell therapy and DMPK research. However, the definition of differentiated hepatocytes is not really clear. Here, we review the studies of hepatocyte differentiation and discuss the trait of the cells.

View full abstract

Immunosuppressive drugs are now widely used as preventive treatments of allograft rejection in organ transplantation. Monitoring of drug concentration reduces the frequency of acute graft rejection but over 10% of renal transplant recipients experience at least one acute rejection within the first 6 months after transplantation. In addition, drug toxicity, especially due to over immunosuppression seriously hamper long-term success. For further optimization of immunesuppressive therapy, new monitoring strategy is required and pharmacodynamics strategies could constitute novel approaches for optimization of immunosuppressive drugs. In this review I summarized those trials mainly based on our own studies and proposed useful biomarkers including drug target cytokines and lymphocyte proliferation.The studies show that the degree of immunosuppression can be quantitated in each transplant recipient. Future prospective studies will confirm the potentiality of these markers toward optimized individually-tailored immunosuppressive treatment. In addition, these biomarkers could be also helpful for weaning or minimization of immunosuppressive therapy and the selection of the treatment candidates.

View full abstract

It takes long time and huge cost to develop new drugs. However, average successrate from first-in human to registration in all therapeutic areas is approximately 11%. Notably,success rate in oncology area is 5% or less. Development of new drugs carries out under generalconsideration for clinical trials(ICH E8)and therapeutic guidelines. The treatment landscape ofoncology is rapidly changing. Antineoplastic drugs have been developed from non-specificcytotoxic drugs to specific molecular targeted agents sometimes with companion diagnostics. Theantineoplastic drug should be developed in each type of cancer and this article shows how to developantineoplastic drugs and current treatment landscape in lung cancer, colorectal cancer, and breastcancer as representative cancer types. In addition, development of immunotherapy is emerging inmalignant melanoma and probably beyond this indication.Recently, Ipilimumab (an antibody against cytotoxic T-lymphocyte-associated antigen 4［CTLA-4］) and Vemurafenib (BRAF kinase inhibitor) were approved by US Food and DrugAdministration(FDA). New treatment of immunotherapies incorporates in this article, including theanti-PD-1 antibody which can inhibit newly identified immune check point.

View full abstract

Subcutaneous adipose tissue, normally found throughout body, has been used as abiological material for correction of various tissue defects in plastic, cosmetic and reconstructivesurgery fields. Lipoaspiration or resection of adipose tissue and fat grafting are routinely carried outin clinic with minimal risk. Adipose tissue is well-vascularized, and fat cells have a relatively longlifespan. Adipose tissue is now recognized as an important endocrine and secretory organ of variousbioactive cytokines to regulate homeostasis of human body. The accumulated evidence attractsmuch attention in regenerative medicine as cell source for gene/cell therapy. There are two methodsin the preparation of adipose tissue-derived proliferative cells. One method is preparation fromstromal vascular fraction, which is obtained as sediment by the centrifugation of collagenasedigestedfat tissue and is the most common technique. The other is from the floating fraction afterthe centrifugation to obtain mature fat cells. The cells are further purified by ceiling culture. In thisreview, we introduce the outline of preparation of primary adipocytes and our therapeutic approachof an adipose tissue-based lifelong and risk-manageable treatment for patients with intractableserum protein deficiencies.

View full abstract