Column

Column

How the important people view?

To lead iPS cell research for clinical applications (1) -All 2 episodes-

Dr. Masayo Takahashi

In ophthalmology, regenerative medicine using pluripotent stem cells will be introduced into clinical settings out of laboratory soon. Dr. Takahashi Masayo, expected as one of those who will be leading this field of research, first saw stem cells in the US about 15 years ago, and immediately became convinced that such cells can be used for retinal regeneration. She was the first researcher in the world who succeeded in generating retinal cells and retinal pigment epithelial cells (RPECs), first from ES cells, and then from iPS cells. She is now busy preparing to put retinal regenerative medicine into practice. She is confident that many patients will be saved by regenerative medicine, and continues her research.

Interviewer :
Transplantation of RPECs differentiated from iPS cells by Dr. Takahashi and her group is expected to be the first clinical application of iPS cells.

Takahashi :
We conducted transplantation studies in 2004 in which RPECs derived from monkey ES cells were transplanted into rats, and became convinced that transplantation of ES cell-derived RPECs can be used for treatment without safety problems. However, we have to accumulate data to prove that the technique is safe before applying it at a clinical level in humans. It is now scientifically at a stage where we are able to conduct clinical studies, however, we have many time-consuming works to be done before meeting the regulatory requirements, although we do not have any problem of changing policies or which renders the treatment impossible.

Interviewer :
In November 2010, the "Guidelines for Clinical Research using Human Stem Cells" were revised, to provide a framework for clinical research towards regenerative medicine using iPS cells. There seem to have been some changes in regulations.

Takahashi :
Yes, there are. The revised regulations on the use of iPS cells do not put large obstacles in the way of forwarding our research to a clinical stage. Scientists on their part worked the government to revise the guidelines based on their forecast about future development of research, and I should say that the revision this time was made by joint work of scientists and the government.
On the occasion of the international symposium on human iPS cell research held about two and half a year ago, we mentioned that we would be the first to work on clinical applications of iPS cells. We estimated that arrangements for guidelines necessary for promoting research would be delayed and this would be an obstacle to our advancing to a clinical stage. At that time, ES or iPS cells were not covered by the "Guidelines for Clinical Research using Human Stem Cells" at all.
It was stipulated in the original guidelines that they were to be reviewed after five years of enforcement, but they were revised after four years. It seems that the Ministry of Health, Labour and Welfare shows an attitude different from that before toward stem cell research, and is ready to promote it. iPS cells may have helped it. It seems to me that iPS cells pave the way for advancing stem cell research.

Interviewer :
In the year 2011, the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the Ministry of Economy, Trade and Industry will jointly launch a project called "Highway to the Realization of Regenerative Medicine" to continuously promote R&D for realization of regenerative medicine, and there will be a more powerful supporting system. Under such circumstances, are clinical trials still a long way off?

Takahashi :
We conduct clinical research according to the Medical Act, where we are to verify, in collaboration with doctors, the safety of a treatment in a small number of patients. It seems that we will proceed to this stage without problem, but will not do so easily to the subsequent stage of clinical trials to which the Pharmaceutical Affairs Law is applicable. We will not need much time to accumulate data, but will need much money to perform clinical trials.
I hear the market size in the US is approximately five times that in Japan, while costs for clinical trials in Japan are approximately 1.5 times those in the US. We are discussing where to conduct clinical trials, taking account of cost-effectiveness.

Photo:Dr. Masayo Takahashi

Dr. Masayo Takahashi

Interviewer :
Recently, you have concluded an agreement for development with Japan Tissue Engineering Co., LTD (J-TEC), which had created autologous cultured epidermis Is it for clinical trials in the future?

Takahashi :
We have not reached such a stage of cooperation, and for the moment J-TEC provides us with technical assistance on a non-profit basis. J-TEC spent enormous amount of money to conduct a clinical trial on the skin transplantation. However, at the last stage of listing in the National Health Insurance drug price list, applicable patients were limited and accordingly profits to be gained were reduced. If this situation will not change, I think regenerative medicine will not take root in Japan.
J-TEC says "Clinical research using iPS cells is like F1 race. We are to develop for the first time an innovative technology, and we know that this activity of development will not pay" They may have an option of not entering clinical trials, taking account of the costs that the trials will incur. We have to have a large company who has a high funding ability participate in our clinical trials from their early stage. How to realize it is our problem for the moment. It seems that companies tend to be more and more interested in such activities.

Interviewer :
You mean that they know that it is not yet at a stage of manufacturing a popular car, but expect that it will be so in the near future.

Takahashi :
We have been at a stage of clinical research where 5 cases have been treated since several years, and at this stage we have been leading the research in cooperation with J-TEC. It covers the whole process of collecting patients' skin cells, generating iPS cells and differentiating them into RPECs, and transplanting them into the patients. At present, it takes about 6 months to complete this process There are several hundreds of thousands of patients with AMD (age-related macular degeneration) who are susceptible of being treated with this technique, and in order to make this treatment widely available, it is necessary that companies enter this field and commercialize it. In the field of regenerative medicine in ophthalmology, we have already a vision of commercializing cornea and then retina as a next target.
Fortunately, on the Kobe Port Island, where RIKEN Center for Developmental Biology (CDB) is located, there are Cell Processing Center on the other side of the railway track who is producing cells for clinical use, next to it The Institute of Biomedical Research and Innovation hospital, the only institution in Japan that specializes in advanced medicine, Kobe City Medical Center General Hospital, and more than 200 medical companies invited. This is a very promising area being developed in the framework of Kobe's Medical Industry Development Project.

Interviewer :
Do you think many patients will come to Kobe in several years?

Takahashi :
The Medical Industry Development Project includes a plan for receiving patients from other Asian countries. We are confident that we have best-quality RPECs in the form of cell sheets and hope to distribute them widely in Japan as well as in other countries.

Interviewer :
Your technology to generate RPECs has been developed to a stage where we can call it a "manufacturing process", but what is the highlight of this process?

Takahashi :
It is how to make a sheet of cells. This is a technique to be claimed in a patent. Fortunately, we have an exclusive team comprising of experts in stem-cell patent. As for stem cells, if the differentiation process has been a little changed, or only a part of generated cells is different, we can apply for a different patent.
It is very difficult for researchers alone to survive in such a competitive field without support of patent experts. One who spread his net earlier is the winner. It is also the case for clinical trials, and it is important to perform them as early as possible and take control of the market.


Interviewer :
Furugori Etsuko
Interview date : February 18, 2011

  1. 1
  2. 2

Dr. Masayo Takahashi

Physician, Doctor of Medicine, and team leader at the Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN (the Institute of Physical and Chemical Research).

1986 : Graduated from the School of Medicine, Kyoto University
1986 : Medical intern at the Department of Ophthalmology, the School of Medicine, Kyoto University
1987 : Physician in Kansai Electric Power Hospital
1988 : Student of the Doctoral course in ophthalmology and visual science at the Graduate School of Medicine, Kyoto University
1992 : Assistant at the Department of Ophthalmology, the School of Medicine, Kyoto University
1995 : Research fellow at the Salk Institute, USA
1997 : Assistant at the Department of Ophthalmology, the School of Medicine, Kyoto University
2001 : Assistant Professor at the Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital(leader of the Retinal Regeneration Project)
2006 : Team leader at RIKEN (the Institute of Physical and Chemical Research) Kobe Institute October 2006 : Team leader at the Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN; Part-time physician at the Department of Ophthalmology, Kobe City Center General Hospital
2008 : Visiting Vice Director at the Department of Ophthalmology, Institute of Biomedical Research and Innovation hospital (concurrent post); Leader of the Visual Regeneration Research Group at the Institute of Biomedical Research and Innovation laboratory
2009 : Visiting Associate Professor for courses of advanced international medicine at the Graduate School of Medicine, Kyoto University
January 2010 : Visiting Professor in the Center for iPS Cell Research and Application (CiRA), Kyoto University (concurrent post)

Movie

See more

Page top

Movie

Movie

  • MEXT
  • Japan Science and Technology Agency
Page top