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Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration
BACKGROUND: We have previously reported that xeno-transplanted human ESC-derived retinas are able to mature in the immunodeficient retinal degeneration rodent models, similar to allo-transplantations using mouse iPSC-derived retina. The photoreceptors in the latter developed outer segments and forme...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354559/ https://www.ncbi.nlm.nih.gov/pubmed/30502055 http://dx.doi.org/10.1016/j.ebiom.2018.11.028 |
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author | Tu, Hung-Ya Watanabe, Takehito Shirai, Hiroshi Yamasaki, Suguru Kinoshita, Masaharu Matsushita, Keizo Hashiguchi, Tomoyo Onoe, Hirotaka Matsuyama, Take Kuwahara, Atsushi Kishino, Akiyoshi Kimura, Toru Eiraku, Mototsugu Suzuma, Kiyoshi Kitaoka, Takashi Takahashi, Masayo Mandai, Michiko |
author_facet | Tu, Hung-Ya Watanabe, Takehito Shirai, Hiroshi Yamasaki, Suguru Kinoshita, Masaharu Matsushita, Keizo Hashiguchi, Tomoyo Onoe, Hirotaka Matsuyama, Take Kuwahara, Atsushi Kishino, Akiyoshi Kimura, Toru Eiraku, Mototsugu Suzuma, Kiyoshi Kitaoka, Takashi Takahashi, Masayo Mandai, Michiko |
author_sort | Tu, Hung-Ya |
collection | PubMed |
description | BACKGROUND: We have previously reported that xeno-transplanted human ESC-derived retinas are able to mature in the immunodeficient retinal degeneration rodent models, similar to allo-transplantations using mouse iPSC-derived retina. The photoreceptors in the latter developed outer segments and formed synapses with host bipolar cells, driving light responses of host retinal ganglion cells. In view of clinical application, here we further confirmed the competency of human iPSC-derived retina (hiPSC-retina) to mature in the degenerated retinas of rat and monkey models. METHODS: Human iPSC-retinas were transplanted in rhodopsin mutant SD-Foxn1 Tg(S334ter)3LavRrrc nude rats and two monkeys with laser-induced photoreceptor degeneration. Graft maturation was studied by immunohistochemistry and its function was examined by multi-electrode array (MEA) recording in rat retinas and visually-guided saccade (VGS) in a monkey. FINDINGS: A substantial amount of mature photoreceptors in hiPSC-retina graft survived well in the host retinas for at least 5 months (rat) to over 2 years (monkey). In 4 of 7 transplanted rat retinas, RGC light responses were detected at the grafted area. A mild recovery of light perception was also suggested by the VGS performance 1.5 years after transplantation in that monkey. INTERPRETATION: Our results support the competency of hiPSC-derived retinas to be clinically applied for transplantation therapy in retinal degeneration, although the light responses observed in the present models were not conclusively distinguishable from residual functions of degenerating host retinas. The functional analysis may be further elaborated using other models with more advanced retinal degeneration. |
format | Online Article Text |
id | pubmed-6354559 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-63545592019-02-07 Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration Tu, Hung-Ya Watanabe, Takehito Shirai, Hiroshi Yamasaki, Suguru Kinoshita, Masaharu Matsushita, Keizo Hashiguchi, Tomoyo Onoe, Hirotaka Matsuyama, Take Kuwahara, Atsushi Kishino, Akiyoshi Kimura, Toru Eiraku, Mototsugu Suzuma, Kiyoshi Kitaoka, Takashi Takahashi, Masayo Mandai, Michiko EBioMedicine Research paper BACKGROUND: We have previously reported that xeno-transplanted human ESC-derived retinas are able to mature in the immunodeficient retinal degeneration rodent models, similar to allo-transplantations using mouse iPSC-derived retina. The photoreceptors in the latter developed outer segments and formed synapses with host bipolar cells, driving light responses of host retinal ganglion cells. In view of clinical application, here we further confirmed the competency of human iPSC-derived retina (hiPSC-retina) to mature in the degenerated retinas of rat and monkey models. METHODS: Human iPSC-retinas were transplanted in rhodopsin mutant SD-Foxn1 Tg(S334ter)3LavRrrc nude rats and two monkeys with laser-induced photoreceptor degeneration. Graft maturation was studied by immunohistochemistry and its function was examined by multi-electrode array (MEA) recording in rat retinas and visually-guided saccade (VGS) in a monkey. FINDINGS: A substantial amount of mature photoreceptors in hiPSC-retina graft survived well in the host retinas for at least 5 months (rat) to over 2 years (monkey). In 4 of 7 transplanted rat retinas, RGC light responses were detected at the grafted area. A mild recovery of light perception was also suggested by the VGS performance 1.5 years after transplantation in that monkey. INTERPRETATION: Our results support the competency of hiPSC-derived retinas to be clinically applied for transplantation therapy in retinal degeneration, although the light responses observed in the present models were not conclusively distinguishable from residual functions of degenerating host retinas. The functional analysis may be further elaborated using other models with more advanced retinal degeneration. Elsevier 2018-11-28 /pmc/articles/PMC6354559/ /pubmed/30502055 http://dx.doi.org/10.1016/j.ebiom.2018.11.028 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Tu, Hung-Ya Watanabe, Takehito Shirai, Hiroshi Yamasaki, Suguru Kinoshita, Masaharu Matsushita, Keizo Hashiguchi, Tomoyo Onoe, Hirotaka Matsuyama, Take Kuwahara, Atsushi Kishino, Akiyoshi Kimura, Toru Eiraku, Mototsugu Suzuma, Kiyoshi Kitaoka, Takashi Takahashi, Masayo Mandai, Michiko Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration |
title | Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration |
title_full | Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration |
title_fullStr | Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration |
title_full_unstemmed | Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration |
title_short | Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration |
title_sort | medium- to long-term survival and functional examination of human ipsc-derived retinas in rat and primate models of retinal degeneration |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354559/ https://www.ncbi.nlm.nih.gov/pubmed/30502055 http://dx.doi.org/10.1016/j.ebiom.2018.11.028 |
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