Masayo Takahashi, M.D. Ph.D.
John Muir once said: “In the eternal youth of Nature, you may renew your own”. However, since then stem cell research has come some way and is capturing the imagination of the public in a way that few other fields of science have. The cloning of Dolly the sheep by Sir Ian Wilmut in 1996 was the first historic landmark event in this field, and in 2007 Prof. Shinya Yamanaka received the Nobel prize in Physiology or Medicine for demonstrating for the first time that adult human cells could be reprogrammed into induced pluripotent stem (iPS) cells. Inspired by this, many researchers have begun to focus on using stem cells in degenerative diseases.
Prof. Masayo Takahashi is a stem cell biologist at the RIKEN Center for Developmental Biology in Japan. Her research has pioneered a promising stem-cell based treatment approach for age-related macular degeneration (AMD), which is the most common cause of blindness in the elderly population. Recently, she performed the world’s first induced pluripotent stem cell-derived retinal cell transplant into humans, marking another milestone in stem cell research.
Age related macular degeneration is the degeneration of the macula, an oval-shaped area near the center of the retina, which contains a very high density of receptor cells that perceive color vision. The macula is thus responsible for the central, high-resolution, color vision that is possible in good light; and this kind of vision is impaired if the macula is damaged. While it does not result in complete blindness, a loss of central vision can make it hard to recognize faces, drive, read, or perform other activities of daily life. Currently there is no curative treatment for this disease, and this motivates Prof. Takahashi and her team as their research continues to pursue Takahashi’s vision for stem cells in the clinic. “Our laboratory focuses on doing research that contributes to the welfare of patients, not the publication of papers or pursuit of money and fame,” she explains. “Our goal is patient happiness. I only care about the treatment; I don’t care about papers at all. Sometimes people say that I should publish more papers, but I’m interested in creating the shortest path to treatments for patients.“
Prof. Takahashi received her M.D. Ph.D. from Kyoto University and is an ophthalmologist by training. She performed extensive clinical and research work at Kyoto University and the Salk Insititute, CA and has been a principal investigator and clinician at RIKEN for over 11 years. She received the 2014 Stem cell person of the year award for pioneering vision and pluripotent stem cell clinical research. Nature magazine named her as one of five Scientists to Watch in 2014, and as one of ten People Who Mattered in 2014.
In 2014, a Japanese woman in her 70s is the recipient of the world’s first retinal transplant using retinal tissue generated from stem cells that were derived from the patient’s own skin cells. Since then the team has further developed this exciting therapeutic strategy, so that donor tissue can be used instead of the patient’s own tissue, providing a much more cost-effective approach. In March 2017, the first patient with AMD received an experimental transplant of retinal cells made from induced pluripotent stem cells derived from a healthy donor. This patient was the first in a clinical trial to examine the safety and feasibility of transplanting donor-derived retinal pigment epithelial cells. The study is conducted by the Kobe City Medical Center General Hospital in collaboration with Osaka University Hospital, RIKEN, and the Center for iPS Cell Research and Application at Kyoto University. During the surgery, approximately 250,000 retinal pigment epithelial cells generated from donor-derived iPSCs were transplanted into the patient’s eye. The results of this study were recently published in the prestigious New England Journal of Medicine.
While using cells from healthy donors to generate transplantable retinal pigment epithelial cells can trigger donor-host immune responses, this technique is much more cost effective and thus affordable to patients. Prof. Takahashi believes, that an iPSC-based approach has great potential to become a standard treatment for AMD in future. But for now, the team is relieved that the surgery went smoothly and the patient is recovering well. Their aim is to continue to recruit patients for this trial and perform the procedure in at least 5 patients over the next 2 years to assess its safety, feasibility and success. In addition, they are working on being able to perform transplantation of photoreceptors along with iPS-derived cells within five years, which should not only slow age-related macular degeneration, but could possibly even restore some vision.
Although the team is very excited about this recent promising study, they remain cautiously optimistic. Prof. Takahashi understands that a negative outcome in her small clinical study could scuttle the efforts of other researchers hoping to bring iPS cells to the clinic. However, the work of Prof. Takahashi and her team was extremely rigorous, careful, based on extensive preclinical studies, and government approved; overall a great example of in essence science-based clinical medicine. And it surely offers a glimpse of hope to the public that even though eternal youth is not lurking around the corner, a treatment for age-related macular degeneration and other certain neurodegenerative diseases may be available in the not too distant future.
Researched and written by Jolanda Muenzel