Safety and stable survival of stem-cell-derived retinal organoid for 2 years in patients with retinitis pigmentosa

Yasuhiko Hirami; Michiko Mandai; Sunao Sugita; Akiko Maeda; Tadao Maeda; Midori Yamamoto; Hirofumi Uyama; Satoshi Yokota; Masashi Fujihara; Masataka Igeta; Takashi Daimon; Kanako Fujita; Tomoko Ito; Naoki Shibatani; Chikako Morinaga; Tetsuya Hayama; Aya Nakamura; Kazuki Ueyama; Keiichi Ono; Hidetaka Ohara; Masayo Fujiwara; Suguru Yamasaki; Kenji Watari; Kiyoko Bando; Keigo Kawabe; Atsushi Ikeda; Toru Kimura; Atsushi Kuwahara; Masayo Takahashi; Yasuo Kurimoto

doi:10.1016/j.stem.2023.11.004

Safety and stable survival of stem-cell-derived retinal organoid for 2 years in patients with retinitis pigmentosa

Cell Stem Cell. 2023 Dec 7;30(12):1585-1596.e6. doi: 10.1016/j.stem.2023.11.004.

Authors

Yasuhiko Hirami¹, Michiko Mandai², Sunao Sugita³, Akiko Maeda⁴, Tadao Maeda⁵, Midori Yamamoto⁵, Hirofumi Uyama⁶, Satoshi Yokota⁷, Masashi Fujihara⁷, Masataka Igeta⁸, Takashi Daimon⁸, Kanako Fujita⁹, Tomoko Ito⁹, Naoki Shibatani⁹, Chikako Morinaga¹⁰, Tetsuya Hayama¹¹, Aya Nakamura¹², Kazuki Ueyama¹², Keiichi Ono¹², Hidetaka Ohara¹³, Masayo Fujiwara¹¹, Suguru Yamasaki¹¹, Kenji Watari¹¹, Kiyoko Bando¹³, Keigo Kawabe¹³, Atsushi Ikeda¹¹, Toru Kimura¹⁴, Atsushi Kuwahara¹¹, Masayo Takahashi¹⁵, Yasuo Kurimoto⁷

Affiliations

¹ Department of Ophthalmology, Kobe City Eye Hospital, Kobe 650-0047, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe 650-0047, Japan; Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan. Electronic address: yhirami@kcho.jp.
² Department of Ophthalmology, Kobe City Eye Hospital, Kobe 650-0047, Japan; Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan; Research Center, Kobe City Eye Hospital, Kobe 650-0047, Japan; RIKEN Program for Drug Discovery and Medical Technology Platforms, Yokohama 230-0045, Japan.
³ Department of Ophthalmology, Kobe City Eye Hospital, Kobe 650-0047, Japan; Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan.
⁴ Department of Ophthalmology, Kobe City Eye Hospital, Kobe 650-0047, Japan; Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan; Research Center, Kobe City Eye Hospital, Kobe 650-0047, Japan.
⁵ Department of Ophthalmology, Kobe City Eye Hospital, Kobe 650-0047, Japan; Research Center, Kobe City Eye Hospital, Kobe 650-0047, Japan.
⁶ Department of Ophthalmology, Kobe City Eye Hospital, Kobe 650-0047, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe 650-0047, Japan.
⁷ Department of Ophthalmology, Kobe City Eye Hospital, Kobe 650-0047, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe 650-0047, Japan; Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan.
⁸ Department of Biostatistics, Hyogo Medical University, Nishinomiya 663-8501, Japan.
⁹ Research Center, Kobe City Eye Hospital, Kobe 650-0047, Japan.
¹⁰ RIKEN Program for Drug Discovery and Medical Technology Platforms, Yokohama 230-0045, Japan.
¹¹ Regenerative & Cellular Medicine Kobe Center, Sumitomo Pharma Co. Ltd., Kobe 650-0047, Japan.
¹² Technology Research & Development Division, Sumitomo Pharma Co. Ltd., Kobe 650-0047, Japan.
¹³ Regenerative & Cellular Medicine Office, Sumitomo Pharma Co. Ltd., Tokyo 103-6012, Japan.
¹⁴ Regenerative & Cellular Medicine Kobe Center, Sumitomo Pharma Co. Ltd., Kobe 650-0047, Japan; Regenerative & Cellular Medicine Office, Sumitomo Pharma Co. Ltd., Tokyo 103-6012, Japan.
¹⁵ Department of Ophthalmology, Kobe City Eye Hospital, Kobe 650-0047, Japan.

PMID: 38065067
DOI: 10.1016/j.stem.2023.11.004

Abstract

Transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into retinal disease animal models has yielded promising results, and several clinical trials on iPSC-derived retinal pigment epithelial cell transplantation have confirmed its safety. In this study, we performed allogeneic iPSC-derived retinal organoid sheet transplantation in two subjects with advanced retinitis pigmentosa (jRCTa050200027). The primary endpoint was the survival and safety of the transplanted retinal organoid sheets in the first year post-transplantation. The secondary endpoints were the safety of the transplantation procedure and visual function evaluation. The grafts survived in a stable condition for 2 years, and the retinal thickness increased at the transplant site without serious adverse events in both subjects. Changes in visual function were less progressive than those of the untreated eye during the follow-up. Allogeneic iPSC-derived retinal organoid sheet transplantation is a potential therapeutic approach, and the treatment's safety and efficacy for visual function should be investigated further.

Keywords: clinical study; full-field stimulus threshold testing; induced pluripotent stem cell; regenerative therapy; retinal organoid; retinitis pigmentosa; transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Induced Pluripotent Stem Cells*
Organoids
Retina
Retinitis Pigmentosa* / therapy
Vision, Ocular