Speaking with Masayo Takahashi: Targeting age-related macular degeneration in the first iPSC clinical trial

Written by Freya Leask

In this interview, Masayo Takahashi, Project Leader for Laboratory for Retinal Regeneration at the RIKEN Centre for Developmental Biology (Kobe, Japan), explains the techniques being utilized in the first iPSC clinical trial in humans.

In this interview, Masayo Takahashi, Project Leader for Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology (Kobe, Japan) explains the techniques being utilized in the first induced pluripotent stem cell (iPSC) clinical trial in humans. Dr Takahashi also reveals how they may change when the trial restarts, having been halted in 2015.

Masayo Takahashi (MD, PhD)
Masayo Takahashi MD, PhD is Project Leader of the Laboratory for Retinal Regeneration at RIKEN (Kobe, Japan). She received her MD from Kyoto University (Kyoto, Japan) in 1986, and her PhD in Medicine at the same institution in 1992. After serving as an assistant professor in the Department of Ophthalmology, Kyoto University Hospital, she moved to the Salk Institute (CA, USA) in 1995, where she first learned of the potential of stem cells as a tool for retinal therapy. She returned to the same hospital in 1997, and since 2001 has served as an associate professor at the Translational Research Center (Kyoto, Japan). She joined RIKEN as a team leader of the retinal regeneration team in 2006. Her team started a pilot clinical study of autologous iPS cell-derived RPE cell sheets for exudative aged-related macular degeneration in 2013. The first RPE cell sheet graft was transplanted in September 2014.

Why did you choose age-related macular degeneration as the target for the iPSC therapy?

My research using stem cells began in 1995 and I have been trying to develop a therapy ever since. I researched embryonic stem cells (ESCs) and finally came to study iPSCs. From iPSCs, we can develop different retinal cells, including retinal pigment epithelial (RPE) cells and photoreceptor cells, and we are currently working on a therapy using both of these. However, photoreceptor cells are neurons so it can be difficult to make them work in the body, whereas RPE cells are not so it is easier to develop treatment. We found that RPE cells were most effective in treating age-related macular degeneration, which afflicts many people, so this is the target we chose first. [Ed: A study published in the Lancet in 2014 estimated that 196 million people will suffer from either dry- or wet-type age-related macular degeneration, rising to 288 million in 20401.]

What challenges have you faced in planning and executing the trial?

It’s very difficult to make and maintain good iPSCs, but we have very talented technicians who can make good iPSCs and culture them properly. In the first trial, we made 30 lines of iPSCs from one patient then selected the good iPSCs. The purity of the end product is also very important; there should be no bad cell contamination.

What techniques did you utilize to select the good iPSCs?

We chose the best cell lines by looking at their morphology first. Our technicians are very experienced so by looking at characteristics such as the colors, the smoothness of the cell surface and the dividing speed, they can tell which cells are good and bad. We then confirmed that the cells were good using gene analysis.

In 2015, the trial was halted. What happened, and will any changes be made to the trial design when it starts up again?

The first clinical research was halted because the law for regenerative medicine in Japan changed, but we’re now preparing the next clinical study. We will use three different protocols including allogeneic iPSCs. In the first trial, we used only autologous iPSCs, but next time we will use both. We won’t use immunosuppressive drugs, which is a big challenge when using allogeneic cells, but we will utilize human leukocyte antigen (HLA) typing to minimize any problems this may cause.

What does the future hold for iPSC therapy?

I think it’s very promising. Without a doubt, regenerative medicine will become a big field in the future. In fact, preventative and regenerative medicine will be two big fields, and iPSCs and ESCs have the potential to industrialize the cell therapy field. iPSCs and ESCs can be expanded so we can make many cells for many patients and really build regenerative medicine as an industry.


  • – Research fund from Healios K.K. and Sumitomo Dainippon Pharma Co., Ltd.


  1. Wong WL, Su X, Li X. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. The Lancet Global Health. 2(2), e106 – e116.

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