Genetically engineered stem cell-derived retinal grafts for improved retinal reconstruction after transplantation
| Autor: | Masayo Takahashi, Junki Sho, Jianan Sun, Take Matsuyama, Tomoyo Hashiguchi, Akishi Onishi, Momo Fujii, Ryutaro Akiba, Michiko Mandai, Hung-Ya Tu |
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| Rok vydání: | 2021 |
| Předmět: |
Retinal degeneration
Multidisciplinary Science Retinal Bioengineering Biology medicine.disease Photoreceptor cell Article Cellular neuroscience Cell biology Transplantation chemistry.chemical_compound medicine.anatomical_structure Stem cells research chemistry Retinal ganglion cell Genetically Engineered Mouse medicine Tissue engineering Stem cell Neuroscience |
| Zdroj: | iScience iScience, Vol 24, Iss 8, Pp 102866-(2021) |
| ISSN: | 2589-0042 |
| Popis: | Summary ESC/iPSC-retinal sheet transplantation, which supplies photoreceptors as well as other retinal cells, has been shown to be able to restore visual function in mice with end-stage retinal degeneration. Here, by introducing a novel type of genetically engineered mouse ESC/iPSC-retinal sheet with reduced numbers of secondary retinal neurons but intact photoreceptor cell layer structure, we reinforced the evidence that ESC/iPSC-retinal sheet transplantation can establish synaptic connections with the host, restore light responsiveness, and reduce aberrant retinal ganglion cell spiking in mice. Furthermore, we show that genetically engineered grafts can substantially improve the outcome of the treatment by improving neural integration. We speculate that this leads to reduced spontaneous activity in the host which in turn contributes to a better visual recovery. Graphical Abstract Highlights • Photoreceptors in organoids with bipolar cell-KO can functionally mature in vivo • Photoreceptors in KO grafts form more synapses with host bipolar cells • KO grafts better suppress heightened spontaneous spiking in degenerated retina • Mice transplanted with KO grafts perform better in light-guided behavior test Neuroscience; Cellular neuroscience; Bioengineering; Tissue engineering; Stem cells research |
| Databáze: | OpenAIRE |
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