Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors

Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors

Summary: Pluripotent stem cells can be differentiated into 3D retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioproces...

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Main Authors: Tyler DiStefano, Holly Yu Chen, Christopher Panebianco, Koray Dogan Kaya, Matthew J. Brooks, Linn Gieser, Nicole Y. Morgan, Tom Pohida, Anand Swaroop
Format: Article
Language:English
Published: Elsevier 2018-01-01
Series:Stem Cell Reports
Subjects:
iPSC
embryonic stem cell
in vitro organogenesis
retina development
3-D organoid culture
retinal disease
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671117304873
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spelling doaj-4534fa091fec4dc1be0a867ba423a0b22020-11-25T03:07:18ZengElsevierStem Cell Reports2213-67112018-01-0110130031310.1016/j.stemcr.2017.11.001Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel BioreactorsTyler DiStefano0Holly Yu Chen1Christopher Panebianco2Koray Dogan Kaya3Matthew J. Brooks4Linn Gieser5Nicole Y. Morgan6Tom Pohida7Anand Swaroop8Neurobiology, Neurodegeneration, and Repair Laboratory (N-NRL), National Eye Institute (NEI), National Institutes of Health, Bldg 6/338, 6 Center Drive, Bethesda, MD 20814, USANeurobiology, Neurodegeneration, and Repair Laboratory (N-NRL), National Eye Institute (NEI), National Institutes of Health, Bldg 6/338, 6 Center Drive, Bethesda, MD 20814, USANeurobiology, Neurodegeneration, and Repair Laboratory (N-NRL), National Eye Institute (NEI), National Institutes of Health, Bldg 6/338, 6 Center Drive, Bethesda, MD 20814, USANeurobiology, Neurodegeneration, and Repair Laboratory (N-NRL), National Eye Institute (NEI), National Institutes of Health, Bldg 6/338, 6 Center Drive, Bethesda, MD 20814, USANeurobiology, Neurodegeneration, and Repair Laboratory (N-NRL), National Eye Institute (NEI), National Institutes of Health, Bldg 6/338, 6 Center Drive, Bethesda, MD 20814, USANeurobiology, Neurodegeneration, and Repair Laboratory (N-NRL), National Eye Institute (NEI), National Institutes of Health, Bldg 6/338, 6 Center Drive, Bethesda, MD 20814, USATrans-NIH Shared Resources on Biomedical Engineering and Physical Sciences (BEPS), National Institutes of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bldg 13/3N18B, 13 South Drive, Bethesda, MD 20814, USASignal Processing and Instrumentation Section, Center for Information Technology (CIT), National Institutes of Health, Bldg 12A/2021, 12 South Drive, Bethesda, MD 20814, USANeurobiology, Neurodegeneration, and Repair Laboratory (N-NRL), National Eye Institute (NEI), National Institutes of Health, Bldg 6/338, 6 Center Drive, Bethesda, MD 20814, USA; Corresponding authorSummary: Pluripotent stem cells can be differentiated into 3D retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioprocess using rotating-wall vessel (RWV) bioreactors to culture retinal organoids derived from mouse pluripotent stem cells. Organoids in RWV demonstrate enhanced proliferation, with well-defined morphology and improved differentiation of neurons including ganglion cells and S-cone photoreceptors. Furthermore, RWV organoids at day 25 (D25) reveal similar maturation and transcriptome profile as those at D32 in static culture, closely recapitulating spatiotemporal development of postnatal day 6 mouse retina in vivo. Interestingly, however, retinal organoids do not differentiate further under any in vitro condition tested here, suggesting additional requirements for functional maturation. Our studies demonstrate that bioreactors can accelerate and improve organoid growth and differentiation for modeling retinal disease and evaluation of therapies.http://www.sciencedirect.com/science/article/pii/S2213671117304873iPSCembryonic stem cellin vitro organogenesisretina development3-D organoid cultureretinal disease
collection DOAJ
language English
format Article
sources DOAJ
author Tyler DiStefano
Holly Yu Chen
Christopher Panebianco
Koray Dogan Kaya
Matthew J. Brooks
Linn Gieser
Nicole Y. Morgan
Tom Pohida
Anand Swaroop
spellingShingle Tyler DiStefano
Holly Yu Chen
Christopher Panebianco
Koray Dogan Kaya
Matthew J. Brooks
Linn Gieser
Nicole Y. Morgan
Tom Pohida
Anand Swaroop
Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors
Stem Cell Reports
iPSC
embryonic stem cell
in vitro organogenesis
retina development
3-D organoid culture
retinal disease
author_facet Tyler DiStefano
Holly Yu Chen
Christopher Panebianco
Koray Dogan Kaya
Matthew J. Brooks
Linn Gieser
Nicole Y. Morgan
Tom Pohida
Anand Swaroop
author_sort Tyler DiStefano
title Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors
title_short Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors
title_full Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors
title_fullStr Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors
title_full_unstemmed Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors
title_sort accelerated and improved differentiation of retinal organoids from pluripotent stem cells in rotating-wall vessel bioreactors
publisher Elsevier
series Stem Cell Reports
issn 2213-6711
publishDate 2018-01-01
description Summary: Pluripotent stem cells can be differentiated into 3D retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioprocess using rotating-wall vessel (RWV) bioreactors to culture retinal organoids derived from mouse pluripotent stem cells. Organoids in RWV demonstrate enhanced proliferation, with well-defined morphology and improved differentiation of neurons including ganglion cells and S-cone photoreceptors. Furthermore, RWV organoids at day 25 (D25) reveal similar maturation and transcriptome profile as those at D32 in static culture, closely recapitulating spatiotemporal development of postnatal day 6 mouse retina in vivo. Interestingly, however, retinal organoids do not differentiate further under any in vitro condition tested here, suggesting additional requirements for functional maturation. Our studies demonstrate that bioreactors can accelerate and improve organoid growth and differentiation for modeling retinal disease and evaluation of therapies.
topic iPSC
embryonic stem cell
in vitro organogenesis
retina development
3-D organoid culture
retinal disease
url http://www.sciencedirect.com/science/article/pii/S2213671117304873
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AT hollyyuchen acceleratedandimproveddifferentiationofretinalorganoidsfrompluripotentstemcellsinrotatingwallvesselbioreactors
AT christopherpanebianco acceleratedandimproveddifferentiationofretinalorganoidsfrompluripotentstemcellsinrotatingwallvesselbioreactors
AT koraydogankaya acceleratedandimproveddifferentiationofretinalorganoidsfrompluripotentstemcellsinrotatingwallvesselbioreactors
AT matthewjbrooks acceleratedandimproveddifferentiationofretinalorganoidsfrompluripotentstemcellsinrotatingwallvesselbioreactors
AT linngieser acceleratedandimproveddifferentiationofretinalorganoidsfrompluripotentstemcellsinrotatingwallvesselbioreactors
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AT tompohida acceleratedandimproveddifferentiationofretinalorganoidsfrompluripotentstemcellsinrotatingwallvesselbioreactors
AT anandswaroop acceleratedandimproveddifferentiationofretinalorganoidsfrompluripotentstemcellsinrotatingwallvesselbioreactors
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