Journal of Clinical Medicine (Jul 2020)
HLA-Matched Allogeneic iPS Cells-Derived RPE Transplantation for Macular Degeneration
- 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
Affiliations
- Sunao Sugita
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- Michiko Mandai
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- Yasuhiko Hirami
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- Seiji Takagi
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- Tadao Maeda
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- Masashi Fujihara
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- Mitsuhiro Matsuzaki
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- Midori Yamamoto
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- Kyoko Iseki
- Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
- Naoko Hayashi
- Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
- Ayumi Hono
- Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
- Shoko Fujino
- Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
- Naoshi Koide
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- Noriko Sakai
- Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
- Yumiko Shibata
- Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
- Motoki Terada
- Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
- Mitsuhiro Nishida
- Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
- Hiromi Dohi
- Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8567, Japan
- Masaki Nomura
- Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8567, Japan
- Naoki Amano
- Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8567, Japan
- Hirokazu Sakaguchi
- Department of Advanced Device Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
- Chikako Hara
- Department of Advanced Device Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
- Kazuichi Maruyama
- Department of Innovative Visual Science, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
- Takashi Daimon
- Department of Biostatistics, Hyogo College of Medicine, Nishinomiya 663-8501, Japan
- Masataka Igeta
- Department of Biostatistics, Hyogo College of Medicine, Nishinomiya 663-8501, Japan
- Toshihiko Oda
- Center for Clinical Research and Innovation, Kobe City Medical Center General Hospital, Kobe 650-0047, Japan
- Utako Shirono
- Center for Clinical Research and Innovation, Kobe City Medical Center General Hospital, Kobe 650-0047, Japan
- Misato Tozaki
- Center for Clinical Research and Innovation, Kobe City Medical Center General Hospital, Kobe 650-0047, Japan
- Kota Totani
- Tomey Corporation, Nagoya 451-0051, Japan
- Satoshi Sugiyama
- Tomey Corporation, Nagoya 451-0051, Japan
- Kohji Nishida
- Department of Ophthalmology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
- Yasuo Kurimoto
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- Masayo Takahashi
- Department of Ophthalmology and Kobe City Eye Hospital, Kobe 650-0047, Japan
- DOI
- https://doi.org/10.3390/jcm9072217
- Journal volume & issue
-
Vol. 9,
no. 7
p. 2217
Abstract
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.
Keywords