A regenerative chit-chat with Masayo Takahashi

A regenerative chit-chat with Masayo Takahashi

Marta Paterlini

Published: 11 February 2015

Advances in Regenerative Biology 2015. © 2015 Marta Paterlini. This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 Unported (CC BY 4.0) License (http://creativecommons.org/licenses/by/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for any purpose, even commercially, provided the original work is properly cited and states its license.

Citation: Advances in Regenerative Biology 2015, 2: 27401 - http://dx.doi.org/10.3402/arb.v2.27401

 

An interview with Dr. Masayo Takahashi, Head of the Laboratory for Retinal Regeneration at the RIKEN Center for Developmental Biology, Kobe, Japan.

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Dr. Masayo Takahashi received a PhD from the Kyoto University. After serving as an assistant professor at the Kyoto University Hospital, Dr. Takahashi moved to the Salk Institute, La Jolla, CA, USA, where she discovered the potential of stem cells as a tool for retinal therapy. Dr. Masayo Takahashi is a member of the RIKEN (Rikagaku Kenkyusho) Center for Developmental Biology since 2006.

ARB: Could you tell us a bit about your background? How do you divide your time between research and clinic?

Takahashi: I worked as an ophthalmologist in the Kyoto University Hospital for more than 15 years. After I moved to Kobe, I only see patients who suffer from retinal degenerative diseases in the outpatient clinic in the hospital next to our institute twice a week. Now, I dedicate most of my time to management, and lecturing.

ARB: Your team and you developed techniques to treat age-related macular degeneration in the exudative form. How did it get so far?

Takahashi: Professor Yoshiki Sasai developed a method to make retinal epithelial (RPE) cells from monkey embrionic stem (ES) cells and asked me to prove it. That was the beginning and the biggest step toward the treatment. As an ophthalmologist, I believed the cells could be used for retinal treatment. So, I proved that the cells can treat retinal disease in a rat model. This was the first report of utilizing primate ES cells for any kind of disease. Then, I started the preclinical work, working on methods and materials for clinical use.

ARB: In September, a Japanese woman with a visual impairment became the first person to receive a therapy derived from stem cells known as induced pluripotent stem (iPS) cells.  Now, how do you follow her up, from the clinical point of view and from the more basic research point of view?

Takahashi: We evaluate not only visual acuity but perform many kinds of ophthalmology test, such as OCT (optical coherence tomography that allows analysis of the retina's morphology), retinal sensitivity, tumor formation, retinal photograph, FAG (fluorescein angiography that measures the blood flow in the retina and choroid), and so on. The clinical team follows her up every month up to 6 months and then once every 2 months up to 1 year.

From the basic research point of view, it is interesting if autologous iPS-cell-derived cells truly avoid the immune rejection or not, grafted RPE behavior.

Going forward, a bigger study will be held not with autologous treatment, like now, but with allogeneic treatment.

ARB: Are you optimistic and confident about the current treatment?

Many fear that, should the woman experience serious consequences, iPS cell research could be set back years.

Takahashi: RPE cells have the special characteristics that can warrant safety. People who do not know the advances in the iPS cell generation method, and the RPE cell nature, might think they bear a risk. People who the details beyond iPS and RPE think it is safe and I am quite confident that the cells will not cause any trouble. Indeed, I am rather worried about the surgery, because even ordinary surgeries have much higher risks than with the cells.

ARB: Before the first transplant in humans, in which animals did you perform most of the preliminary studies?

Takahashi: I set the proof of concept in rats, then established tumorigenicity in mice. The surgery was developed in rabbits and monkeys, and we tested immune rejection in monkeys.

ARB: How do you foresee the future for iPS cells?

Takahashi: iPS cells will contribute in many aspects, not only in science but also in society. For example, the potentials of iPS cells have helped to accelerate changes to pharmaceutical law in Japan.

ARB: This amazing achievement of yours could also confirm Japan, recently pestered by a stem cell scandal, as a frontrunner in iPS cell research. Do you think that Japan is ahead in translational stem cell research right now?

Takahashi: Yes, circumstances in Japan are affected by the stem cell scandal somehow. However, there is still big support for regenerative medicine.

For example, the new pharmaceutical law implemented this year is quite a big change that might put Japan in a very good position.

In our case, the first approval of the clinical research was given in August 2013. The transplant was performed only four days after a health ministry committee gave clearance for the human trial. This operation is both a huge milestone and one of the fastest translations from bench to bedside in terms of iPSCs.

Moreover, soon after, recent changes in regulations in Japan's clinical translation pipeline occurred. Therefore, clinical innovations may become even faster.

ARB: The Japanese research has been overshadowed by the STAP cell research fraud earlier this year that had a tragic end for a famous Japanese scientist. How did you deal with this?

Takahashi: Some people worried about the attitude of RIKEN and asked me to reconsider the clinical research, so I replied ‘I will consider it again’. I did not think to hold the first patients’ treatment at all. Indeed, it was tough to manage the skepticism around RIKEN.

Dr. Masayo Takahashi, thank you for the interview.

Marta Paterlini
Email: martapaterlini@nasw.org

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Marta Paterlini

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