학술논문
Self-organization, quality control, and preclinical studies of human iPSC-derived retinal sheets for tissue-transplantation therapy.
Document Type
Article
Author
Watari, Kenji; Yamasaki, Suguru; Tu, Hung-Ya; Shikamura, Masayuki; Kamei, Tatsuya; Adachi, Hideki; Tochitani, Tomoaki; Kita, Yasuyuki; Nakamura, Aya; Ueyama, Kazuki; Ono, Keiichi; Morinaga, Chikako; Matsuyama, Take; Sho, Junki; Nakamura, Miyuki; Fujiwara, Masayo; Hori, Yoriko; Tanabe, Anna; Hirai, Rina; Terai, Orie
Source
Subject
*PHOTORECEPTORS
*QUALITY control
*PLURIPOTENT stem cells
*HUMAN stem cells
*RETINAL degeneration
*HUMAN experimentation
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Language
ISSN
2399-3642
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 transplantation therapy. Toward tissue/organoid transplantation therapy, a quality control method for human iPSC-derived retinal sheet is presented, and its therapeutic potential is demonstrated in preclinical safety and efficacy studies. [ABSTRACT FROM AUTHOR]