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Promotion of research from a broad perspective to take a next step forward (1) -All 3 episodes-

Prof. Makoto Asashima

Photo:Prof. Makoto Asashima

Prof. Makoto Asashima

We had an opportunity to meet and interview Professor Makoto Asashima who is an expert in developmental biology and famous for his discovery of activin, a protein that induces cell differentiation. He shared with us his opinion on the future of iPS cell research, or more generally research on development and differentiation.

Interviewer :
I hear that, in July 2009, you assumed the position of a senior scientist at the Center for Research and Development Strategy (CRDS) of Japan Science and Technology Agency (JST), and made a trip in November 2009 in other countries to survey the situations of iPS and other stem cell research there.
Would you tell us how you find the situations of research and development in other countries? And what is your perspective on the iPS cell or stem cell research in Japan in 5 or 10 years? Is there anything to be done at this moment for the future?Is there anything lacking? What political support will be required?

Asashima :
I think that the creation of iPS cells by Prof. Yamanaka and his colleques in Japan was a great achievement. They first succeeded in generating mouse iPS cells, and then human iPS cells, which are expected to have a variety of clinical applications.
We see various studies made on iPS cells also in USA and other countries. For example, for the techniques for generating these cells, some researchers are trying to use low-molecular weight compounds as an alternative to the four factors used by Prof. Yamanaka. And others are trying to find applications of iPS cells. There are different directions of basic research.
I suppose that iPS cell research will make significant progress in the field of drug discovery. Experiments with disease models developed using patient-derived iPS cells will promote research and development in this field.

"Standardization" to promote the future development of research

Prof. Makoto Asashima(Sketch by Katsuaki Sato)

Prof. Makoto Asashima
(Sketch by Katsuaki Sato)

Asashima :
When we talk about the future of iPS cell research, we have to keep in mind that there are a variety of methods for generating iPS cells and the generated cells have different characteristics. So far, we have no established methods or conditions for generation of iPS cells, their culture, and the maintenance of pluripotency. It is important to have some objective indicators to define iPS cells for the future development of research. In this point, some other countries have already experiences for ES and other somatic stem cells.

Specifically, when the four genes are transferred into the cell nucleus, they randomly go into different areas of a chromosome, cause changes in the original functions of the cell genome, or there might be epigenetic modifications of the genes.
It is necessary to study whether iPS cells show different characteristics, when they have been generated under different conditions : medical history, age, and sex of the donnor, the type of the organ from which the cells are derived, conditions of cell collection and culture, e.g. presence or absence of serum and feeder cells. And it is possible that iPS cells generated under the same conditions give colonies that have different characteristics between each other. When we clone cells from different colonies grown to a certain size and grow these cloned cells by several passages, the cells derived from a cell cloned at the center of a colony and those from a cell cloned at the periphery of the colony may give different characteristics. iPS cells may lose their pluripotency after many passages, and we may get many types of iPS cell-like cells.

For the development of iPS cell research, it is important to set objective indices to define iPS cells : the degree of gene expressions, state of cells, expression of a certain gene and tendency to be specific tissue cells. It is necessary to control the quality of cells in terms of reproducibility and set standards for the future of iPS cell research.

Toward standardization

Prof. Makoto Asashima

Asashima :
In fact, standardization is not an easy task. Scientists in some other countries have experiences for ES cells and are able to take better strategies.
Harvard University is trying to standardize iPS and ES cells in a way that they distribute free of charge the cells generated at the University to as many scientists as possible in the world to collect necessary data. The more the number of scientists who use the cells is, the more the data obtained are. And it is important to share the data among the scientists with the aid of bioinformatics. We can say that, in general, the cells that have been used by many scientists will most often be the standard cells. I think it possible that iPS cells generated by Japanese scientists will be the world standard, if Japan takes the international initiative in standardization.

Interviewer :
Why is it so difficult in Japan?

Asashima :
In Japan, the main policy of handling intellectual properties is to protect them from access of the third parties. Meanwhile, the Japanese government has begun to loosen the conditions, and the question is how to generalize this tendency of loosening the conditions.
We had also very strict ethical standards for human ES cell research, which is partly attributable to the trend of that time. I think it is important to give a message that "the cells are available under such and such conditions", in order to promote scientific research with a long-term vision. If conditions are too strict for research facilities and handling of cells, researchers will not be able to afford the cost and have to give up the research project. We need to improve the conditions in a transparent manner vis-a-vis the Japanese public after explaining them the situation and obtaining an informed consent from them.

Both ES and somatic stem cells are important

Asashima :
For promoting iPS cell research, it is also important to promote research on ES and somatic stem cells. In other countries, there are research projects on both iPS cells and other stem cells(ES cells, somatic stem cells including adipose- and bone marrow-derived ones) to compare these cells and better understand the characteristics of iPS cells. Japan is no longer a leader in mesenchymal stem cell research as it used to be.


Interviewed by Miwako Honma (supervisor of iPS Trend website), Katsuaki Sato,Yuki Konagaya(Japan Science Technology Agency)
Published on 25 January, 2010

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Prof. Makoto Asashima

Professor Emeritus, Former Vice President, member of the Board of Directors, and Research Professor of the University of Tokyo
Senior Research Fellow of the Center for Research and Development Strategy, Japan Science and Technology Agency
Chief of Organ Development Research Laboratory, the National Institute of Advanced Industrial Science and Technology

1972 : Graduated from the Doctoral Course of the School of Science, the University of Tokyo (Received a doctorate in science)
Researcher at Institut fur Chemie und Biochemie, Freie Universitat Berlin Associate Professor and Professor at the Faculty of Liberal Arts, Yokohama City University
1993 : Professor at the Graduate School of Arts and Sciences, the University of Tokyo
1996 : Professor at the Department of Language and Information Sciences, the Graduate School of Arts and Sciences, the University of Tokyo
2003 : Director of the Department of Language and Information Sciences/Director of the Graduate School of Arts and Sciences, the University of Tokyo
2005 : Vice President of the Science Council of Japan
From 2007 to March 2008 : President and Vice Principal of the University of Tokyo

President of the Japanese Society of Developmental Biologists
President of the Zoological Society of Japan
President of the Molecular Biology Society of Japan
President of the Japanese Society for Biological Sciences in Space
Steering Committee and Council Member of the Japan Society for Cell Biology
Steering Committee Member of the International Society of Developmental Biologists
Board Member of the Japanese Society for Tissue Engineering
Board Member of the Japanese Society for Regenerative Medicine
Board Member of the Japanese Society of Inflammation and Regeneration
Member of the New York Academy of Sciences
Editorial Board Member of journals : "Development, Growth & Differentiation", "Zoological Science", and "Cell Structure and Function"
Vice Editorial Chief of the "International Journal of Developmental Biology"

He specializes in developmental biology, and has been and is working on organogenesis (from an egg to larva), cell growth and differentiation. He identified activin, a mesoderm-inducing factor, in 1988 for the first time in the world, and contributed to establishing a system of inducing organs.

Awards :
1990 : The Prize of the Zoological Society of Japan
1990 : Inoue Prize for Science
1990 : Man of the Year (USA, ABI)
1994 : Kihara Memorial Yokohama Foundation for the Advancement of Life Sciences
1994 : Philipp Franz von Siebold-Preis (German Government)
1999 : Toray Science and Technology Prize
2000 : Academic Award for Medical and Pharmaceutical Research of the Mochida Memorial Foundation
2000 : The Naito Foundation Merit Award for Advancement of Science
2000 : Professor Kei Arima Memorial Award of the Japan Bioindustry Association
2001 : Uehara Prize
2001 : The Medal with Purple Ribbon
2001 : Imperial Award of the Japan Academy
2002 : The Medal of the Prince Hitachi Prize for Comparative Oncology
2008 : Erwin-Stein-Preis
2008 : Person of Cultural Merit

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