In collaboration with Shinya Yamanaka, the 2012 Nobel Laureate in Bio/Medicine, who dedifferentiated somatic cells into pluripotent stem cells, i.e., induced pluripotent stem cells, Masayo Takahashi found an effective method for induced pluripotent stem cells to generate retinal epithelial cells, and in September 2014, he advanced the first human clinical trial of epithelial cells induced by induced pluripotent stem cells. The experiment was conducted in a patient in his seventies with age-related macular degeneration, who had largely lost his vision and was unlikely to recover. After a year of research, the preliminary results of this high-profile experiment have finally been announced.
This study evaluated the feasibility of transplanting a series of retinal pigment epithelial cells differentiated from induced pluripotent stem cells in patients with neovascular age-related macular degeneration. Induced pluripotent stem cells were derived from epidermal fibroblasts from two patients with advanced macular degeneration of neovascular age-increasing age and differentiated into retinal pigment epithelial cells, and the origin of both induced pluripotent stem cells and retinal pigment epithelial cells has been extensively tested. In one of the patients, retinal pigment epithelial cells with surgical removal of the neovascular layer and implantation of autologous induced pluripotent stem cell differentiation were found to be intact 1 year after surgery, and the transplanted series of cells was found to be intact, the best corrected visual acuity was neither improved nor worsened, and cystoid macular edema remained.
The study, published by NEJM and endorsed by Science, illustrates that the use of pluripotent stem cells to replace the destroyed eye tissue in age-related macular degeneration does prevent the disease from progressing, although it does not improve the patient's visual function. The greatest significance of the first treatment in vivo using pluripotent stem cells is that although the effectiveness is not yet certain, it is an encouraging milestone in confirming the safety of the use of induced pluripotent stem cells in humans. In addition, the publication of experimental details is beneficial for other research teams to treat diseased or necrotic tissues through mature tissue-derived pluripotent surrogate cells.
In the Science article, some of the problems encountered in clinical trials and further plans for epithelial cells from induced pluripotent stem cell differentiation are mentioned. During the experiment of the second patient, pluripotent stem cells were unstable and there was a risk of carcinogenesis, and the experiment was suspended due to safety considerations. The experiment is still progressing, and the clinical trial of 5 patients that has been approved will be carried out soon, instead of the previous induction of autopluripotent stem cells for each patient, Masayo Takahashi will use a single volunteer donor to establish a pluripotent stem cell bank, and apply it to patients in the early stage of age-related macular degeneration after the technology matures. Researchers and the public are full of hope for induced pluripotent stem cells, but existing experiments have shown that induced pluripotent stem cells can help, but cannot completely reverse the development of the disease.
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.