Self-organization, quality control, and preclinical studies of human iPSC-derived retinal sheets for tissue-transplantation therapy
bioRxiv(2023)
摘要
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.
### Competing Interest Statement
This work was funded by AMED under grant number JP21bm0204002 (M.T., S.K.) and by Sumitomo Pharma Co., Ltd. (Sumitomo). K.W., S.Y., T.Ka., H.A., T.T., Y.K., A.N., K.U., K.O., M.F., Y.H., A.T., R.H., O.T., O.O., H.O., T.H., A.I., D.N., K.M., A.Ki., and A.Ku. are employed by Sumitomo. T.Ki. is a board member of Sumitomo. S.K. has a scientific consulting role for Sumitomo. M.T. and M.M. have received research funding from Sumitomo. The authors are co-inventors on patent applications. The remaining authors declare no competing interests.
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