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Cells
Volume 10
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10.3390/cells10092489
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Review

Inducible Pluripotent Stem Cells to Model and Treat Inherited Degenerative Diseases of the Outer Retina: 3D-Organoids Limitations and Bioengineering Solutions

by
Massimiliano Andreazzoli
1,*,†,
Ivana Barravecchia
2,3,†,
Chiara De Cesari
1,
Debora Angeloni
3 and
Gian Carlo Demontis
2,*
1
Department of Biology, University of Pisa, 56127 Pisa, Italy
2
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
3
Institute of Life Sciences, Scuola Superiore Sant’Anna, 56124 Pisa, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2021, 10(9), 2489; https://doi.org/10.3390/cells10092489
Submission received: 18 August 2021 / Revised: 12 September 2021 / Accepted: 15 September 2021 / Published: 20 September 2021
(This article belongs to the Special Issue Neural Stem Cell Systems to Study Brain Development and Diseases)
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Abstract

Inherited retinal degenerations (IRD) affecting either photoreceptors or pigment epithelial cells cause progressive visual loss and severe disability, up to complete blindness. Retinal organoids (ROs) technologies opened up the development of human inducible pluripotent stem cells (hiPSC) for disease modeling and replacement therapies. However, hiPSC-derived ROs applications to IRD presently display limited maturation and functionality, with most photoreceptors lacking well-developed outer segments (OS) and light responsiveness comparable to their adult retinal counterparts. In this review, we address for the first time the microenvironment where OS mature, i.e., the subretinal space (SRS), and discuss SRS role in photoreceptors metabolic reprogramming required for OS generation. We also address bioengineering issues to improve culture systems proficiency to promote OS maturation in hiPSC-derived ROs. This issue is crucial, as satisfying the demanding metabolic needs of photoreceptors may unleash hiPSC-derived ROs full potential for disease modeling, drug development, and replacement therapies.
Keywords: iPSC; retinal organoids; inherited retinal degenerations; photoreceptors; disease modeling; transplantation; subretinal space; aerobic glycolysis; bioengineering iPSC; retinal organoids; inherited retinal degenerations; photoreceptors; disease modeling; transplantation; subretinal space; aerobic glycolysis; bioengineering
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MDPI and ACS Style

Andreazzoli, M.; Barravecchia, I.; De Cesari, C.; Angeloni, D.; Demontis, G.C. Inducible Pluripotent Stem Cells to Model and Treat Inherited Degenerative Diseases of the Outer Retina: 3D-Organoids Limitations and Bioengineering Solutions. Cells 2021, 10, 2489. https://doi.org/10.3390/cells10092489

AMA Style

Andreazzoli M, Barravecchia I, De Cesari C, Angeloni D, Demontis GC. Inducible Pluripotent Stem Cells to Model and Treat Inherited Degenerative Diseases of the Outer Retina: 3D-Organoids Limitations and Bioengineering Solutions. Cells. 2021; 10(9):2489. https://doi.org/10.3390/cells10092489

Chicago/Turabian Style

Andreazzoli, Massimiliano, Ivana Barravecchia, Chiara De Cesari, Debora Angeloni, and Gian Carlo Demontis. 2021. "Inducible Pluripotent Stem Cells to Model and Treat Inherited Degenerative Diseases of the Outer Retina: 3D-Organoids Limitations and Bioengineering Solutions" Cells 10, no. 9: 2489. https://doi.org/10.3390/cells10092489

APA Style

Andreazzoli, M., Barravecchia, I., De Cesari, C., Angeloni, D., & Demontis, G. C. (2021). Inducible Pluripotent Stem Cells to Model and Treat Inherited Degenerative Diseases of the Outer Retina: 3D-Organoids Limitations and Bioengineering Solutions. Cells, 10(9), 2489. https://doi.org/10.3390/cells10092489

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