Microfluidic organ-on-a-chip model of the outer blood–retinal barrier with clinically relevant read-outs for tissue permeability and vascular structure

Arık, Yusuf B.; Buijsman, Wesley; Loessberg-Zahl, Joshua; Cuartas-Vélez, Carlos; Veenstra, C. N.; Logtenberg, Sander; Grobbink, Anne M; Bergveld, Piet; Gagliardi, Giuliana; Hollander, Anneke I. den; Bosschaart, Nienke; Berg, Albert van den; Passier, Robert; Meer, Andries D. van der

doi:10.1039/d0lc00639d

Cited by 54 publications

(52 citation statements)

References 61 publications

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“…Microfluidic technologies are well-suited for the study of retinal degenerative diseases, as well as the development of novel therapies, by developing models that mimic the physiological environment at the retinal microscale. Organ-on-a-chip platforms (reviewed in [ 61 , 62 ]) have been recently developed by multiple groups using retinal stem and progenitor cells (SCs) [ 63 , 64 , 65 , 66 ] or organoids [ 67 , 68 , 69 , 70 ] to recapitulate the retinal cellular niche in both healthy and disease states. Some existing systems use 3D, organotypic systems that integrate explanted retina to measure tissue viability and cytotoxicity [ 71 ], while others examine the delivery of therapeutic compounds [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

A Microfluidic Eye Facsimile System to Examine the Migration of Stem-like Cells

2022

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Millions of adults are affected by progressive vision loss worldwide. The rising incidence of retinal diseases can be attributed to damage or degeneration of neurons that convert light into electrical signals for vision. Contemporary cell replacement therapies have transplanted stem and progenitor-like cells (SCs) into adult retinal tissue to replace damaged neurons and restore the visual neural network. However, the inability of SCs to migrate to targeted areas remains a fundamental challenge. Current bioengineering projects aim to integrate microfluidic technologies with organotypic cultures to examine SC behaviors within biomimetic environments. The application of neural phantoms, or eye facsimiles, in such systems will greatly aid the study of SC migratory behaviors in 3D. This project developed a bioengineering system, called the μ-Eye, to stimulate and examine the migration of retinal SCs within eye facsimiles using external chemical and electrical stimuli. Results illustrate that the imposed fields stimulated large, directional SC migration into eye facsimiles, and that electro-chemotactic stimuli produced significantly larger increases in cell migration than the individual stimuli combined. These findings highlight the significance of microfluidic systems in the development of approaches that apply external fields for neural repair and promote migration-targeted strategies for retinal cell replacement therapy.

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Section: Discussionmentioning

confidence: 99%

A Microfluidic Eye Facsimile System to Examine the Migration of Stem-like Cells

2022

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“…150 This unique model enabled 3D co-cultures of monolayers of human retinal pigment epithelium cells with human endothelial cells lining a microvessel. 151 In addition, microvessels demonstrated a well-defined geometry and physiological permeability, which increased in a dose-dependent manner with oxidative stress exposure, making this a useful model for the study of age-related macular degeneration.…”

Section: Functional Readoutsmentioning

confidence: 99%

Microfluidics in vascular biology research: a critical review for engineers, biologists, and clinicians

et al. 2022

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“…The addition of these cells to retinal organoids would likely require assembloid type technology to bring together cells from different developmental lineages, which was pioneered in brain organoids [ 177 ]. Recently, a model of outer-blood-retinal barrier on-a-chip has been described combining RPE and endothelial cells in a microfluidic chamber [ 178 ].…”

Section: Introductionmentioning

confidence: 99%

A look into retinal organoids: methods, analytical techniques, and applications

Afanasyeva

Corral-Serrano²,

Garanto

et al. 2021

Cell. Mol. Life Sci.

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Inherited retinal diseases (IRDs) cause progressive loss of light-sensitive photoreceptors in the eye and can lead to blindness. Gene-based therapies for IRDs have shown remarkable progress in the past decade, but the vast majority of forms remain untreatable. In the era of personalised medicine, induced pluripotent stem cells (iPSCs) emerge as a valuable system for cell replacement and to model IRD because they retain the specific patient genome and can differentiate into any adult cell type. Three-dimensional (3D) iPSCs-derived retina-like tissue called retinal organoid contains all major retina-specific cell types: amacrine, bipolar, horizontal, retinal ganglion cells, Müller glia, as well as rod and cone photoreceptors. Here, we describe the main applications of retinal organoids and provide a comprehensive overview of the state-of-art analysis methods that apply to this model system. Finally, we will discuss the outlook for improvements that would bring the cellular model a step closer to become an established system in research and treatment development of IRDs.

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Microfluidic organ-on-a-chip model of the outer blood–retinal barrier with clinically relevant read-outs for tissue permeability and vascular structure

Abstract: This organ-on-a-chip device of the outer blood retinal barrier will allow future studies of complex disease mechanisms and treatments of visual disorders using clinically relevant endpoints in vitro.

Cited by 54 publications

References 61 publications

A Microfluidic Eye Facsimile System to Examine the Migration of Stem-like Cells

A Microfluidic Eye Facsimile System to Examine the Migration of Stem-like Cells

Microfluidics in vascular biology research: a critical review for engineers, biologists, and clinicians

A look into retinal organoids: methods, analytical techniques, and applications

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