Shinya Yamanaka, the 2012 Nobel Prize winner in Physiology or Medicine, created pluripotent stem cells, iPS cells, from differentiated somatic cells by introducing foreign genes. Masayo Takahashi, who collaborated with him, found an effective method to generate retinal pigment epithelial cells from induced pluripotent stem cells, and in September 2014, she advanced the world's first clinical trial using induced pluripotent stem cells to induce epithelial cells from a patient with age-related macular degeneration, a patient in his seventies who had basically lost his vision and was unlikely to recover. This much-anticipated experiment, which has undergone one year of research, has finally announced preliminary results.
This study evaluated the feasibility of transplanting a series of retinal pigment epithelium cells differentiated from induced pluripotent stem cells in patients with neovascular age-related macular degeneration. Induced pluripotent stem cells were derived from epidermal fibroblasts of two late-stage neovascular age-related macular degeneration patients, differentiated into retinal pigment epithelium cells, and the sources of induced pluripotent stem cells and retinal pigment epithelium cells were extensively tested. In one of the patients, the neovascular layer was surgically removed and autologous induced pluripotent stem cell-derived retinal pigment epithelium cells were transplanted. At 1 year post-surgery, it was found that the transplanted series of cells were still intact, the best corrected visual acuity did not improve or worsen, and the macular cystic edema still existed.
The results of this study, published in NEJM andvouched for by Science, show that: replacing the damaged ocular tissue in age-related macular degeneration with pluripotent stem cells, while not improving the patients’ visual function, did indeed prevent the disease from progressing. As the first instance of using pluripotent stem cells for therapeutic purposes within the human body, its greatest significance lies in: despite the effectiveness being uncertain, it has been confirmed that the use of induced pluripotent stem cells is safe within the human body, a reassuring milestone. Moreover, the publication of the experimental details will facilitate other research teams in treating lesions or necrotic tissue with pluripotent cells derived from mature tissue sources.
Some of the problems encountered in clinical trials of epithelial cells differentiated from induced pluripotent stem cells and further plans are mentioned in the Science article. In the experiment on the second patient, pluripotent stem cells showed instability, posing a risk of cancer, and the experiment was terminated for safety reasons. The experiment is still ongoing, and the next step is to conduct a clinical trial on five approved patients, changing from the previous method of inducing pluripotent stem cells from each patient to a single volunteer donor to establish a stem cell library, and to apply it to early patients with age-related macular degeneration after technical maturity. Researchers and the public are hopeful about induced pluripotent stem cells, but existing experiments all show that induced pluripotent stem cells can help to a certain extent, but cannot completely reverse the development of the disease. High桥雅代 reminds the public that the understanding of induced pluripotent stem cells should be realistic, and induced pluripotent stem cells may not be as effective as everyone expects.
Original source:
Dennis Normile. iPS cell therapy reported safe. Science 2017; 355, 1109-1110. DOI: 10.1126/science.355.6330.1109
Michiko Mandai, et al. Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration. N Engl J Med 2017; 376:1038-1046. DOI 10.1056/NEJMoa1608368.