Induced pluripotent stem (iPS) cells have radically changed medical research. Because they can be transformed into cells from various tissues, they have been observed in a wide range of fields, such as regenerative medicine and drug research.
At the end of March 2022, Dr. Shinya Yamanaka, winner of the 2012 Nobel Prize in Medicine and Physiology, retired from the position of Director of the Center for iPS Cell Research and Application at Kyoto University (CiRA), the leading center for iPS cell research. center in Japan. He was replaced by Dr. Jun Takahashi, also from Kyoto University.
Why change director at this time? Furthermore, what is the current state of iPS cells, the issues surrounding them and the prospects for the future? The Sankei Shimbun asked the two directors in an interview.
Outgoing Director, Dr. Shinya Yamanaka: “The Biggest Decision of My Life”
How do you feel when you retire after 12 years of leadership at CiRA?
For me, this is probably one of the biggest decisions of my life. However, unlike when the center was created, and I was the only teacher, the young generation of that time became the best researchers in the world and now.
Many take over. It is a happiness that exceeds my expectations, and I am very happy to be able to pass the baton with complete peace of mind.
What is the reason for the change?
iPS cells have finally moved from clinical trials to practical application. Therefore, rather than continuing with me as a basic and fundamental research student, I thought it appropriate to have people like Prof. Jun Takahashi (successor to the leadership) who aims for clinical application by himself, to advance the institute.
I would like Professor Takahashi to build the iPS cell research center in his own way.
What’s next for you?
As Chairman of the iPS Cell Research Foundation, which was established two years ago, I will continue to play a liaison role with iPS cell technology companies.
There’s also the fact that I want to continue doing the pure research that I haven’t been able to do as a director. I am happy to have more time for research, but I am also very aware that rehabilitation (to regain my senses) is necessary.
Why will the president stay while the director is retiring?
The research institute has received a lot of support in the form of taxes and donations. I believe this presents high expectations for iPS cells.
In the future, cooperation with companies will be crucial. And I thought it was essential that the president continue to fulfill these responsibilities as a bridge between the foundation and the companies.
What is the biggest challenge towards practical application?
It’s funding. Research takes place over a long period of time, and the closer you get to the goal, the more funding you need.
There are still more than 10 projects in the clinical stage, but the real challenge is ahead of us. From now on, companies will be the main players. But it depends on whether the funds will continue, and the foundation will support research as much as possible.
What type of research will you be conducting in the future?
A gene that I discovered while studying in the United States about 15 years ago seems to be involved in the root of life phenomena, but the big picture is unclear. I would like to use iPS cells as a tool to clarify it.
Additionally, there have been a series of reports indicating that the genes used to make iPS cells are rejuvenated by shortening the working period. This interests me a lot and I would like to explore this question further.
What is the goal of iPS research?
Practical application may be a goal, but there is no end to pure research. And there is no end goal as new discoveries come out one after another.
In this sense, research will continue regularly. I hope I can continue this in my remaining research life and connect it to the next generation.
Incoming Director, Dr. Jun Takahashi: “Take the next step with quality improvements”
What do you think about stepping into the role of director?
Since I’ve been assistant to Professor Yamanaka as deputy principal, I don’t have to worry about sudden changes. However, I think there will be more external communication work.
Is there anything you would like to say to Dr. Yamanaka?
It was a unique career, rewarded with a Nobel Prize. I think it was difficult because not only was he the director of the center, but he also founded, directed and nurtured the iPS research itself.
First of all, I would like to thank you for your hard work. I would like Professor Yamanaka to release some of his burden and have the chance to focus on his research.
And I can’t wait to see the many young people who will be inspired by him.
How do you plan to run the center?
Because I was here with Professor Yamanaka when the institute started from scratch, I understand his role well. Our general principle of making iPS cell technology available to the world and to people will not change when I take on the role of director.
When this institute was established, the clinical implementation of iPS cells was the most important issue. But it was done.
In the future, we envision both vertical and horizontal development. Vertical development means improving iPS cells for clinical use. It’s a linear effort to make even better cells. Our institute will lead with advanced technology.
Horizontal development is the expansion of clinical practice. I myself have transplanted nerve cells derived from iPS cells into patients with Parkinson’s disease. But clinical practice has also been carried out for diseases of the eyes, heart and blood.
We want to extend these applications. Together with various research institutes, we hope to expand the use and eventually make it available even in a typical hospital.
How is the operation of the institute going so far?
We have fulfilled our first mission of clinical achievement, and our facilities and staff have steadily improved. Well, I think we got a passing grade. Dr. Yamanaka successfully took off, and we are now in regular flight.
The decade of government financial support will end this year. In this sense, our physical expansion will come to an end and we will move on to the next stage of qualitative improvement.
How will you use your unique experience?
Professor Yamanaka is a researcher. And I’m a clinician who’s been a brain surgeon for 20 years. I know hands-on treatment strategies, and how to interact with companies and regulators. By taking advantage of these assets, I can take advantage of my experiences.
There’s a lot to do and it seems like a lot of work.
There is no choice but to do so. Researchers and directors are the same in terms of social contribution. We hope to serve the world by developing new treatment methods and creating a vibrant research environment for young people.
The history and future of iPS cells
iPS cells, first developed in 2006, are produced by introducing a special gene into cells taken from an organism’s skin or blood and “initializing” it into a state similar to a fertilized egg that can change and grow into various cells.
What is expected is a regenerative medicine that transplants cells and tissues made from iPS cells into the affected area and treats them. The government has provided support in the order of about 110 billion yen (845 million USD) over a 10-year period from 2013 to 2022.
Since 2014, clinical application studies have been conducted for various conditions such as eye diseases, Parkinson’s disease, heart failure, cancer and spinal cord injuries.
Most of the iPS cells used in research are provided by the Kyoto University iPS Cell Research and Application Center, which produces and stores them. The project was transferred in 2020 to the iPS CiRA Foundation, also at Kyoto University, and now also supplies the cells overseas.
Additionally, researchers are reproducing diseases with iPS cells made from cells from patients with refractory diseases such as amyotrophic lateral sclerosis (ALS) to develop and test the effects of various drugs.
The biggest challenge in marketing is cost. According to the foundation, it costs about ￥40 million JPY (307,000 USD) to collect human blood and make iPS cells. When converted into various cells for transplantation, it costs ￥60 to ￥100 million JPY (about $460,000 to 760,000 USD) for a single person.
The foundation hopes to improve manufacturing efficiency and reduce the cost of production to around 3 million yen (US$23,000).
Dr Shinya Yamanaka graduated from Kobe University Medical School in 1987 and Osaka City University Graduate School in 1993. This native of Osaka Prefecture, born in 1962, became a professor at Kyoto University in 2004, before starting as a senior researcher at the Gladstone Institutes in the United States. United States in 2007. In 2010, he became director of the iPS Cell Research Institute at Kyoto University. In 2020, he was president of the iPS Cell Research Foundation of the same university. He received the Order of Culture and the Nobel Prize in Physiology or Medicine in 2012.
Dr Jun Takahashi became the Director of the iPS Cell Research and Application Center at Kyoto University in 2022. Prior to serving as Director, he served as Deputy Director of the iPS Cell Research Institute for 30 years. A native of Hyogo Prefecture, born in 1961, he graduated from Kyoto University School of Medicine in 1986 where he trained in neurosurgery. He completed the doctoral program at the Graduate School of Kyoto University in 1993. In addition to his work in various positions at Kyoto University, he was a researcher at the Salk Institute for Biological Studies. In 2018, he received the award from the Japan Society for Regenerative Medicine.
(Read the story in Japanese on this link.)
Author: The Sankei Shimbun