Why you should care
Because Masayo Takahashi may bring us much closer to being able to grow a new heart or kidney — custom-made for each patient — if her trial of a new stem cell therapy succeeds.
It’s hard not to be struck by Masayo Takahashi’s confidence — from her clear, steady tone to her ultramarine blazer, one of the many colorful pieces she sports to avoid “being boring.” “I don’t want to be a common, everyday person,” the ophthalmologist said from her office at the RIKEN Center for Developmental Biology in Kobe, Japan.
That boldness is well-suited to the leader of the first-ever human clinical study of a stem cell therapy that could make it possible to grow replacements for diseased organs, custom-made for each patient. Launched last August, the trial involves six patients with macular degeneration, a leading cause of blindness among the elderly that affects an estimated 20,000 to 25,000 people worldwide. It occurs when blood vessels invade and ravage the retina, a layer of tissue that lines the inner surface of the eye.
The breakthrough technique could make it possible to grow replacements for diseased organs, custom-made for each patient.
The stem cells used in the study have a complicated name — induced pluripotent stem cells, or iPSCs — but what they’re capable of is relatively straightforward: They resemble embryonic stem cells and can mature into any type of tissue. Kyoto University geneticist Shinya Yamanaka reported in Cell that he could turn mouse and human skin cells into iPSCs by adding just four genes — earning him a Nobel Prize in 2012.
In the clinical study, Takahashi will remove a tiny sample of skin from the upper arm and reprogram the cells to iPSCs. A set of proteins will transform them into retinal pigment epithelial cells (RPECs), which will then be planted behind the damaged region of the retina. The study’s main objective is to show that the cells are safe; later trials will focus on making the treatment more effective. If all goes well, iPSCs could be in common use within a decade, at least in Japan.
iPSCs sidestep both the ethical pitfalls of embryonic stem cells and immune rejection, as the cells are the patient’s own. But some studies have shown that iPSCs can form tumors. Takahashi, a longtime iPSC expert, insists the cells are safe. Patients and stem cell researchers around the world certainly hope so. “The entire field is watching this study very closely,” said Uri Ben-David, a Ph.D. student in the Hebrew University of Jersualem’s Department of Genetics. “If this study fails… it’s going to be a very serious setback for later iPS cell studies.”
What keeps Takahashi going in the face of such skepticism? Her patients, who urge her to “move faster” toward developing a treatment for macular degeneration. “They tell me, ‘I wish to see my grandchildren’s face’ or ‘I would like to read again,’” she said.
Some studies have shown that iPSCs can form tumors. Takahashi insists the cells are safe.
Coupled with her sense of compassion is a healthy competitive streak. Growing up in bustling, free-spirited Osaka, Takahashi strove to be at the top of her class. And her decision to become a doctor was in part the result of wanting to prove she had what it took to land a spot in Kyoto University’s highly selective medical school.
During her ophthalmology rotation, the plucky medical student fell in love with the human eye — and never looked back. “It’s a very interesting organ and very beautiful inside,” she gushed. “I love the retina.”
After earning an M.D. and a Ph.D., Takahashi headed to San Diego’s Salk Institute for Biological Studies, where she began working with neural stem cells. She then switched her focus to embryonic stem cells, becoming the first to use them to generate RPECs. But she stopped short of developing a therapy; it would have required immunosuppressant drugs, which would have been too risky for her elderly patients.
When Takahashi began her own lab at RIKEN, she heard that Yamanaka had generated iPSCs from human skin cells. The two began “intimately collaborating,” she said, which allowed her to complete a preclinical trial that used the iPSC technique to generate RPECs from adult primate skin cells. “It was very exciting,” Takahashi said.
Takahashi took the helm as project leader as her lab prepared for a clinical study. A self-professed “organizer,” she presented the preclinical data so carefully and convincingly that the project received approval from every regulatory committee.
Credit also goes to the Japanese government, which recently pushed through bills to set new research guidelines and poured billions of dollars into iPSC studies. The public also hails Yamanaka as a national hero. “I want us, Japan, to dominate the world in the area of therapies using iPS cells,” Takahashi told Bloomberg. “The government is opening one door after another.”
Some worry that Takahashi’s preclinical data has yet to be published — hardly unusual for human studies — but “this is so new that one might feel a little more comfortable if that work were published,” said Paul Knoepfler, an associate professor at the UC Davis School of Medicine. “I do have some concerns about whether the field is going too fast,” he blogged. Takahashi said her lab is currently preparing to publish the preclinical data.
But the procedure for macular degeneration requires only a few iPSC-derived cells, reducing the chances that a tumor will grow, Ben-David said. Moreover, according to Takahashi, the tumors seen in other labs are often a result of improper growth conditions, emphasizing that iPSC cultivation in her lab is “severely controlled.”
“Most people think iPS cells are too dangerous to use,” she said. “Once we prove the safety of iPS cell treatment, it will make a big impact. Even if we can’t expect a very high efficacy from the beginning, we should start anyway.”