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Self-organization, quality control, and preclinical studies of human iPSC-derived retinal sheets for tissue-transplantation therapy by Kenji Watari; Suguru Yamasaki; Hung-Ya Tu; Masayuki Shikamura; Tatsuya Kamei; Hideki Adachi; Tomoaki Tochitani; Yasuyuki Kita; Aya Nakamura; Kazuki Ueyama; Keiichi Ono; Chikako Morinaga; Take Matsuyama; Junki Sho; Miyuki Nakamura; Masayo Fujiwara; Yoriko Hori; Anna Tanabe; Rina Hirai; Orie Terai; Osamu Ohno; Hidetaka Ohara; Tetsuya Hayama; Atsushi Ikeda; Daiki Nukaya; Keizo Matsushita; Masayo Takahashi; Akiyoshi Kishino; Toru Kimura; Shin Kawamata; Michiko Mandai; Atsushi Kuwahara is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract Three-dimensional retinal organoids (3D-retinas) are a promising graft source for transplantation therapy. We previously developed self-organizing culture for 3D-retina generation from human pluripotent stem cells (hPSCs). Here we present a quality control method and preclinical studies for tissue-sheet transplantation. Self-organizing hPSCs differentiated into both retinal and off-target tissues. Gene expression analyses identified the major off-target tissues as eye-related, cortex-like, and spinal cord-like tissues. For quality control, we developed a qPCR-based test in which each hPSC-derived neuroepithelium was dissected into two tissue-sheets: inner-central sheet for transplantation and outer-peripheral sheet for qPCR to ensure retinal tissue selection. During qPCR, tissue-sheets were stored for 3–4 days using a newly developed preservation method. In a rat tumorigenicity study, no transplant-related adverse events were observed. In retinal degeneration model rats, retinal transplants differentiated into mature photoreceptors and exhibited light responses in electrophysiology assays. These results demonstrate our rationale toward self-organizing retinal sheet tran

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Author

Kenji Watari; Suguru Yamasaki; Hung-Ya Tu; Masayuki Shikamura; Tatsuya Kamei; Hideki Adachi; Tomoaki Tochitani; Yasuyuki Kita; Aya Nakamura; Kazuki Ueyama; Keiichi Ono; Chikako Morinaga; Take Matsuyama; Junki Sho; Miyuki Nakamura; Masayo Fujiwara; Yoriko Hori; Anna Tanabe; Rina Hirai; Orie Terai; Osamu Ohno; Hidetaka Ohara; Tetsuya Hayama; Atsushi Ikeda; Daiki Nukaya; Keizo Matsushita; Masayo Takahashi; Akiyoshi Kishino; Toru Kimura; Shin Kawamata; Michiko Mandai; Atsushi Kuwahara

Publisher

Springer Science and Business Media LLC

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)