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Researchers for the future

Trying to regenerate the kidney, pancreas and liver (1)-All 2 episodes-

Dr. Kenji Osafune

"The kidney does not regenerate when destroyed by a disease. Why?" It was this question that led Dr. Osafune to be a researcher in this field. After working as clinician in nephrology who treated many patients suffering from intractable diseases, he came to study regenerative biology under Prof. Makoto Asashima. His attitude is always that he does not hesitate to tackle any difficult question, and has made remarkable achievements in research for regeneration of not only the kidney but also the pancreas and the liver.

Photo:Dr. Kenji Osafune

Dr. Kenji Osafune

Interviewer :
You are dealing with three organs that are most difficult to regenerate, aren't you?

Osafune :
In our department, about a half in number of the research fellows are dealing with the kidney, and a half of the remaining half or a quarter is with the pancreas and the other quarter with the liver. In more than 40% of the patients with kidney diseases, their diseases are caused by diabetes. Thus, clinically, the two organs, the kidney and the pancreas, are inseparable. On the other hand, in the intractable disease called "autosomal dominant polycystic kidney disease" (ADPKD), a disease that led me to work on kidney regeneration, liver tissues are also transformed into cysts, and some patients die with liver failure. In order to understand and treat this disease, I found it necessary to study the liver too. I had such motivations, which were conformable to the policy of the institute, so I began to study the three organs.

Interviewer :
How is the situation of research for regeneration of these organs in the world?

Osafune :
Any of these organs is not easy to regenerate. Especially for the kidney, there are not many reports on regeneration of their constituent cells from ES cells or iPS cells. For the pancreas and the liver, there are many reports on regeneration of immature cells, and we see there only part of their functions reproduced as compared to the original functions in our bodies.

Interviewer :
What you find is the background for which there are not many researchers working on regeneration of the kidney?

Osafune :
There are more than 300 thousand dialyzed patients in Japan, and the amount of medical expenses for dialysis occupies 4% of the total amount. In this context, research in this field seems to be highly needed. On the other hand, we do not know yet much of the kidney as compared to other organs. And it has a complex structure and mechanism of development. Thus many people think that the kidney will not be dealt with in regenerative medicine. Will we be able to treat these patients with kidney cell transplantation? Or, will we have to prepare a tree-dimensional organ to treat them? We do not know yet. I have an impression that there are many researchers who assume that it will be difficult, and hesitate to work in this field.
In such circumstances, I have been and am studying always kidney regeneration since the start of my research, and will be also. I keep the same policy.
When I began to think about kidney regeneration, I did not have any idea about how to organize my research. I then thought that I would have to study the mechanism of development of the kidney to be able to reproduce the organ after the model of the process of development that I understand. So I went to study developmental biology under Prof. Asashima at the University of Tokyo.

Interviewer :
You are a medical doctor, and you must have been very courageous to begin to study developmental biology at the graduate school of science, and have had many difficulties to clear, mustn't you?

Osafune :
When I was working in a hospital in Hyogo Prefecture, I happened to see a poster on the lecture titled "Organogenesis from undifferentiated cells" by Prof. Asashima, and on that day I finished my work earlier and went to Kyoto to attend the lecture. I was really inspired by the lecture, and found that it was what I was looking for. I thought I must do it, and I could not help telling it to Prof. Asashima. After the lecture I waited him in front of the anteroom to ask him if he would accept me at the graduate school and study in his lab. Prof. Asashima had already succeeded in generating kidneys in vitro from undifferentiated frog cells, using the growth factor activin.

Dr. Kenji Osafune

I began to study as doctoral student at the graduate school. At that time I was already 29 years old after working as clinician for four years after graduated from school of medicine. I was several years older than other students coming from the department of science, and was a little anxious about my future. I was working there as a graduate student for three years and as a post-doc for two years, during which period I was mainly studying generation of the kidney from mouse ES cells. Then, Prof. Asashima recommended me to go to study under Prof. Melton at Harvard University.
In the Melton's lab, the organ studied for regeneration was not the kidney but the pancreas. So I hesitated a little, but I could imagine that if I would learn how to organize research for organ regeneration in his lab dealing with the pancreas that was more studied than the kidney, I would be able to apply what I have learned there to my research for kidney regeneration, and I decided to go there to work. One year before I went there, 17 human ES cell lines were established in the Melton's lab. At that time, under the President Bush's policy, it was difficult to do research on human ES cells with public research funds, and it is a well-known episode that Prof. Melton was collecting funds in his own way to promote human ES cell research.
I was one of the first researchers who induced differentiation of human ES cells in the Melton's lab.

Interviewer :
What did you find difficult in dealing with human ES cells?

Osafune :
One thing was that it took more time to grow human ES cells than mouse ES cells, and the other was that these cells were more susceptible to infection with microorganisms such as mycoplasma. In addition, we found later that cell lines obtained were not uniform in their characteristics, and it was difficult to deal with them in experiments.


Interviewer :
Furugori Etsuko
Interview date : January 17, 2012

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Dr. Kenji Osafune

Associate Professor, Department of Cell Growth and Development, Center for iPS Cell Research and Application, Kyoto University

In 1971 he was born in Hyogo Prefecture. In 1996 he graduated from Faculty of Medicine, Kyoto University. He was a clinician in nephrology. In 2003 he finished the doctoral course at the Graduate School of Science, The University of Tokyo. He was granted a doctor degree in science. From 2000 to 2005 he was studying development and regeneration of the kidney under Prof. Makoto Asashima at The University of Tokyo. From 2005 to 2008 he was working on kidney regeneration from human ES and iPS cells under Prof. Douglas A. Melton at Harvard University. From 2008 he is working at the Centre for iPS Research and Application, Kyoto University.

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