Genetically engineered stem cell-derived retinal grafts for improved retinal reconstruction after transplantation.

Bioengineering Cellular neuroscience Neuroscience Stem cells research Tissue engineering

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
20 Aug 2021
Historique:
received: 12 01 2021
revised: 23 05 2021
accepted: 14 07 2021
entrez: 19 8 2021
pubmed: 20 8 2021
medline: 20 8 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34409267
doi: 10.1016/j.isci.2021.102866
pii: S2589-0042(21)00834-8
pmc: PMC8361135
doi:

Types de publication

Journal Article

Langues

eng

Pagination

102866

Informations de copyright

© 2021 The Authors.

Déclaration de conflit d'intérêts

There is potential competing interest. The corresponding author is currently filing for a patent regarding the genetically modified retinal organoids. Information of Patent applicant: RIKEN, SUMITOMO DAINIPPON PHARMA CO., LTD name of inventors: Michiko MANDAI, Masayo TAKAHASHI, Suguru YAMASAKI application number: PCT/JP2017/042238 status of application: national phase specific aspect of manuscript covered in patent application: The phenotype of retinal grafts with reduced inner cell population and the probability of improved results following retinal transplantation are covered by the above patent.

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Auteurs

Take Matsuyama (T)

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Hyogo, Japan.

Hung-Ya Tu (HY)

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Osaka, Japan.

Jianan Sun (J)

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.

Tomoyo Hashiguchi (T)

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.

Ryutaro Akiba (R)

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.

Junki Sho (J)

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.

Momo Fujii (M)

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.

Akishi Onishi (A)

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.

Masayo Takahashi (M)

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Hyogo, Japan.

Michiko Mandai (M)

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Hyogo, Japan.

Classifications MeSH