HLA-Matched Allogeneic iPS Cells-Derived RPE Transplantation for Macular Degeneration

• Main Authors: Sunao Sugita, Michiko Mandai, Yasuhiko Hirami, Seiji Takagi, Tadao Maeda, Masashi Fujihara, Mitsuhiro Matsuzaki, Midori Yamamoto, Kyoko Iseki, Naoko Hayashi, Ayumi Hono, Shoko Fujino, Naoshi Koide, Noriko Sakai, Yumiko Shibata, Motoki Terada, Mitsuhiro Nishida, Hiromi Dohi, Masaki Nomura, Naoki Amano, Hirokazu Sakaguchi, Chikako Hara, Kazuichi Maruyama, Takashi Daimon, Masataka Igeta, Toshihiko Oda, Utako Shirono, Misato Tozaki, Kota Totani, Satoshi Sugiyama, Kohji Nishida, Yasuo Kurimoto, Masayo Takahashi
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Journal of Clinical Medicine
• Subjects: HLA; immune reactions; macular degeneration; iPS cells; retina; transplantation
• Online Access: https://www.mdpi.com/2077-0383/9/7/2217

Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-graft cells immune reaction (LGIR) tests using graft RPE and the patient’s blood cells. In all five of the cases that underwent iPS-RPE transplantation, the presence of graft cells was indicated by clumps or an area of increased pigmentation at 6 months, which became stable with no further abnormal growth in the graft during the 1-year observation period. Adverse events observed included corneal erosion, epiretinal membrane, retinal edema due to epiretinal membrane, elevated intraocular pressure, endophthalmitis, and mild immune rejection in the eye. In the one case exhibiting positive LGIR tests along with a slight fluid recurrence, we administrated local steroid therapy that subsequently resolved the suspected immune attacks. Although the cell delivery strategy must be further optimized, the present results suggest that it is possible to achieve stable survival and safety of iPS-RPE cell transplantation for a year.