News & Views : "Japanese researchers are using stem cells to cure retinal degeneration"
In Kobe, Japan, Dr Masayo Takahashi and her colleagues are investigating the therapeutic potential of using autologous stem cells to cure retinal disease1. In 2015, Dr Takahashi received the prestigious Ogawa-Yamanaka Prize in Stem Cell Biology. Together with her team at the Riken Institute’s Centre for Developmental Biology in Kobe, she recently performed the first transplant of cells derived from induced pluripotent stem cells (iPSCs) into a human patient. Last month, Dr Takahashi visited Liège to speak at our monthly GIGA conference series.
Figure 1. Sectional view of a healthy eye and an eye with age-related macular degeneration (AMD) ⁴
Diseases associated with retinal degeneration such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) can lead to severe vision loss (Figure 1). Current therapeutic strategies focus primarily on slowing disease progression; however, treating end-stage retinal degeneration has proven to be quite difficult. Therefore, transplantation of stem cells is a promising new strategy for restoring function in these patients. In recent years, a growing body of evidence suggests that human embryonic stem cells (hESCs) and iPSCscan be used to create retinal tissue. This led Takahashi and her team to ask whether retinal transplantation therapy could be a viable treatment option.
Figure 2. From iPS cells to RPE cell sheet⁴
First, using immunodeficient rats and two monkey models of focal injury-induced retinal degeneration, Takahashi’s team demonstrated that hESC-derived retinal sheets can survive and fully mature to form the structured layers of the retina, including photoreceptors.2 Recently, she took the next logical step and tested the clinical feasibility of this type of transplant in a patient with neovascular AMD in which the retinal pigment epithelium (RPE) is functionally impaired.3 To prevent graft rejection, they generated iPSCs from the patient’s own skin cells. These iPSCs were then differentiated into RPE cells, which were formed into a tissue “sheet” (Figure 2) that was grafted under the patient’s retina (Figure 3). One year after the procedure, the patient showed no signs of transplant rejection. In addition, there were no notable complications or signs of malignant disease. Although the patient’s visual acuity did not improve after the procedure, it did not worsen either, but remained stable. Importantly, the patient’s score on a visual functioning questionnaire (VFQ-25) and the patient’s subjective vision improved after surgery.
Figure 3. Transplantation procedure of RPE cell sheet⁴
Although this research is still in the early days and has been tested in only one patient so far, the results are highly promising, suggesting that stem cells may play an important role in therapeutic transplant approaches. Dr Takahashi notes the vast possibilities that iPSC-based therapies can provide. ‘We believe that one day, nearly every disease will have the potential to be treated using iPSC-derived cells or hESC-derived cells.’
¹ Otake, T. (2017, June 14). Transplants using iPS cells put Riken specialist at forefront of regenerative medicine research. Retrieved November 16, 2017, from https://www.japantimes.co.jp/news/2017/06/14/national/science-health/transplants-using-ips-cells-put-riken-specialist-forefront-regenerative-medicine-research/#.WgqvTNDiaUk
² Shirai, H., et al. (2016). Transplantation of human embryonic stem cell-derived retinal tissue in two primate models of retinal degeneration. Proceedings of the National Academy of Sciences, 113(1), E81-E90.
³ Mandai, M., et al. (2017). Autologous induced stem-cell–derived retinal cells for macular degeneration. New England Journal of Medicine, 376(11), 1038-1046.
⁴ RIKEN – Foundation for Biomedical Research and Innovation (2013). Pilot safety study of iPSC-based intervention for wet-type AMD. Retrieved November 20, 2017 from http://www.riken-ibri.jp/AMD/english/summary.html
Daphne Chylinski, GIGA-CRC In vivo Imaging, Sleep Research Group, PhD student
Bartimée Galvan, GIGA-Molecular Biology of Diseases, Laboratory of Protein Signalling and Interactions, PhD student
Sebastian Schmitz, GIGA-Molecular Biology of Diseases, Laboratory of Cancer Signalling, PhD student
*This “News & Views” item is written as a part of the course “Reading and understanding scientific literature and presentations” offered by GIGA Graduate School