Use of bioreactors for culturing human retinal organoids improves photoreceptor yields

Patrick Ovando-Roche; Emma L West; Matthew J Branch; Robert D Sampson; Milan Fernando; Peter Munro; Anastasios Georgiadis; Matteo Rizzi; Magdalena Kloc; Arifa Naeem; Joana Ribeiro; Alexander J Smith; Anai Gonzalez-Cordero; Robin R Ali

doi:10.1186/s13287-018-0907-0

Use of bioreactors for culturing human retinal organoids improves photoreceptor yields

Patrick Ovando-Roche, Emma L West, Matthew J Branch, Robert D Sampson, Milan Fernando, Peter Munro, Anastasios Georgiadis, Matteo Rizzi, Magdalena Kloc, Arifa Naeem, Joana Ribeiro, Alexander J Smith, Anai Gonzalez-Cordero, Robin R Ali

Medical & Molecular Genetics

King's College London; UCL Institute of Ophthalmology

Research output: Contribution to journal › Article › peer-review

94 Citations (Scopus)

Abstract

BACKGROUND: The use of human pluripotent stem cell-derived retinal cells for cell therapy strategies and disease modelling relies on the ability to obtain healthy and organised retinal tissue in sufficient quantities. Generating such tissue is a lengthy process, often taking over 6 months of cell culture, and current approaches do not always generate large quantities of the major retinal cell types required.

METHODS: We adapted our previously described differentiation protocol to investigate the use of stirred-tank bioreactors. We used immunohistochemistry, flow cytometry and electron microscopy to characterise retinal organoids grown in standard and bioreactor culture conditions.

RESULTS: Our analysis revealed that the use of bioreactors results in improved laminar stratification as well as an increase in the yield of photoreceptor cells bearing cilia and nascent outer-segment-like structures.

CONCLUSIONS: Bioreactors represent a promising platform for scaling up the manufacture of retinal cells for use in disease modelling, drug screening and cell transplantation studies.

Original language	English
Pages (from-to)	156
Journal	Stem cell research & therapy
Volume	9
Issue number	1
DOIs	https://doi.org/10.1186/s13287-018-0907-0
Publication status	Published - 13 Jun 2018

Keywords

Bioreactors/standards
Humans
Organoids/metabolism
Photoreceptor Cells/metabolism
Pluripotent Stem Cells/metabolism
Retina/metabolism

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10.1186/s13287-018-0907-0

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Ovando-Roche, P., West, E. L., Branch, M. J., Sampson, R. D., Fernando, M., Munro, P., Georgiadis, A., Rizzi, M., Kloc, M., Naeem, A., Ribeiro, J., Smith, A. J., Gonzalez-Cordero, A., & Ali, R. R. (2018). Use of bioreactors for culturing human retinal organoids improves photoreceptor yields. Stem cell research & therapy, 9(1), 156. https://doi.org/10.1186/s13287-018-0907-0

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title = "Use of bioreactors for culturing human retinal organoids improves photoreceptor yields",

abstract = "BACKGROUND: The use of human pluripotent stem cell-derived retinal cells for cell therapy strategies and disease modelling relies on the ability to obtain healthy and organised retinal tissue in sufficient quantities. Generating such tissue is a lengthy process, often taking over 6 months of cell culture, and current approaches do not always generate large quantities of the major retinal cell types required.METHODS: We adapted our previously described differentiation protocol to investigate the use of stirred-tank bioreactors. We used immunohistochemistry, flow cytometry and electron microscopy to characterise retinal organoids grown in standard and bioreactor culture conditions.RESULTS: Our analysis revealed that the use of bioreactors results in improved laminar stratification as well as an increase in the yield of photoreceptor cells bearing cilia and nascent outer-segment-like structures.CONCLUSIONS: Bioreactors represent a promising platform for scaling up the manufacture of retinal cells for use in disease modelling, drug screening and cell transplantation studies.",

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AU - Ovando-Roche, Patrick

AU - West, Emma L

AU - Branch, Matthew J

AU - Sampson, Robert D

AU - Fernando, Milan

AU - Munro, Peter

AU - Georgiadis, Anastasios

AU - Rizzi, Matteo

AU - Kloc, Magdalena

AU - Naeem, Arifa

AU - Ribeiro, Joana

AU - Smith, Alexander J

AU - Gonzalez-Cordero, Anai

AU - Ali, Robin R

PY - 2018/6/13

Y1 - 2018/6/13

N2 - BACKGROUND: The use of human pluripotent stem cell-derived retinal cells for cell therapy strategies and disease modelling relies on the ability to obtain healthy and organised retinal tissue in sufficient quantities. Generating such tissue is a lengthy process, often taking over 6 months of cell culture, and current approaches do not always generate large quantities of the major retinal cell types required.METHODS: We adapted our previously described differentiation protocol to investigate the use of stirred-tank bioreactors. We used immunohistochemistry, flow cytometry and electron microscopy to characterise retinal organoids grown in standard and bioreactor culture conditions.RESULTS: Our analysis revealed that the use of bioreactors results in improved laminar stratification as well as an increase in the yield of photoreceptor cells bearing cilia and nascent outer-segment-like structures.CONCLUSIONS: Bioreactors represent a promising platform for scaling up the manufacture of retinal cells for use in disease modelling, drug screening and cell transplantation studies.

AB - BACKGROUND: The use of human pluripotent stem cell-derived retinal cells for cell therapy strategies and disease modelling relies on the ability to obtain healthy and organised retinal tissue in sufficient quantities. Generating such tissue is a lengthy process, often taking over 6 months of cell culture, and current approaches do not always generate large quantities of the major retinal cell types required.METHODS: We adapted our previously described differentiation protocol to investigate the use of stirred-tank bioreactors. We used immunohistochemistry, flow cytometry and electron microscopy to characterise retinal organoids grown in standard and bioreactor culture conditions.RESULTS: Our analysis revealed that the use of bioreactors results in improved laminar stratification as well as an increase in the yield of photoreceptor cells bearing cilia and nascent outer-segment-like structures.CONCLUSIONS: Bioreactors represent a promising platform for scaling up the manufacture of retinal cells for use in disease modelling, drug screening and cell transplantation studies.

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KW - Organoids/metabolism

KW - Photoreceptor Cells/metabolism

KW - Pluripotent Stem Cells/metabolism

KW - Retina/metabolism

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DO - 10.1186/s13287-018-0907-0

M3 - Article

C2 - 29895313

SN - 1757-6512

VL - 9

SP - 156

JO - Stem cell research & therapy

JF - Stem cell research & therapy

IS - 1

ER -

Use of bioreactors for culturing human retinal organoids improves photoreceptor yields

Abstract

Keywords

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