文章基本信息

标题：A Genetic modification that reduces ON-bipolar cells in hESC-derived retinas enhances functional integration after transplantation
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作者：Suguru Yamasaki ; Hung-Ya Tu ; Take Matsuyama 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：1
页码：1-29
DOI：10.1016/j.isci.2021.103657
语种：English
出版社：Elsevier
摘要：SummaryPluripotent stem cell (PSC)-derived retinal sheet transplantedin vivocan form structured photoreceptor layers, contact with host bipolar cells, and transmit light signals to host retinas. However, a major concern is the presence of graft bipolar cells that may impede host-graft interaction. In this study, we used human ESC-retinas with the deletion ofIslet-1(ISL1) gene to achieve the reduced graft ON-bipolar cells after xenotransplantation into end-stage retinal degeneration model rats. Compared with wild-type graft,ISL1−/−hESC-retinas showed better host-graft contact, with indication of host-graft synapse formation and significant restoration of light responsiveness in host ganglion cells. We further analyzed to find out that improved functional integration ofISL1−/−hESC-retinas seemed attributed by a better host-graft contact and a better preservation of host inner retina.ISL1−/−hESC-retinas are promising for the efficient reconstruction of a degenerated retinal network in future clinical application.Graphical abstractDisplay OmittedHighlights•Deletion ofISL1in hESC-retinas resulted in a reduced number of ON-bipolar cells•Photoreceptors inISL1−/−hESC-retinas achieved functional maturationin vivo•ISL1−/−hESC-retinas showed better host-graft contact with putative synapses•ISL1−/−hESC-retinas better restored RGC light responsiveness in degenerated retinaHealth sciences; Medicine; Human; Stem cells research