A treatment within sight: challenges in the development of stem cell-derived photoreceptor therapies for retinal degenerative diseases

Beaver, Davinia; Limnios, Ioannis Jason

doi:10.3389/frtra.2023.1130086

Cited by 2 publications

(1 citation statement)

References 248 publications

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“…A significant challenge is attaining the best possible cell survival and integration in the host retina. Ensuring that RPE cells remain viable and effective over the long term is hampered by their sensitive nature and the possibility of immunological rejection [32], [33]. Moreover, the presence of contaminating cell types may affect the therapeutic efficiency of cell transplantation.…”

Section: Introductionmentioning

confidence: 99%

Dielectrophoretic characterization of peroxidized retinal pigment epithelial cells as a model of age-related macular degeneration

Yadav,

Tivig,

Savopol

et al. 2024

Preprint

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Age-related macular degeneration (AMD) is a prevalent ocular pathology affecting mostly the elderly population. AMD is characterized by a progressive retinal pigment epithelial (RPE) cell degeneration, mainly caused by an impaired antioxidative defense. One of the AMD therapeutic procedures is injecting healthy RPE cells into the subretinal space. For this purpose, there is a need for pure, healthy RPE cell suspensions. In this article, we present an experimental approach to electrically characterize RPE cells, aiming to demonstrate the possibility of separating healthy RPE cells from a mixture of healthy/oxidized cells by dielectrophoresis. In order to find out the relevant conditions to create an in-vitro AMD cellular model, BPEI-1 rat RPE cells were exposed to hydrogen peroxide and evaluated in terms of cell viability by various methods (microscopic imaging, impedance-based real-time cell analysis, MTS assay). Then, healthy and oxidized cells were characterized by recording their dielectrophoretic spectra, based on which electric cell parameters (crossover frequency, membrane conductivity and permittivity, and cytoplasm conductivity) were computed. A COMSOL simulation was performed on a theoretical microfluidic-based dielectrophoretic separation chip using these parameters. By increasing the hydrogen peroxide concentration, we found that the first crossover frequency was shifted toward lower values, and the cell membrane permittivity progressively increased. These changes were attributed to progressive membrane peroxidation since they were diminished when measured on cells treated with the antioxidant N-acetylcysteine. Moreover, the changes in the crossover frequency showed to be enough for the healthy cells to be efficiently separated, as demonstrated by simulations.

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Section: Introductionmentioning

confidence: 99%

Dielectrophoretic characterization of peroxidized retinal pigment epithelial cells as a model of age-related macular degeneration

Yadav,

Tivig,

Savopol

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Dielectrophoretic characterization of peroxidized retinal pigment epithelial cells as a model of age-related macular degeneration

Yadav,

Tivig,

Savopol

et al. 2024

BMC Ophthalmol

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Background Age-related macular degeneration (AMD) is a prevalent ocular pathology affecting mostly the elderly population. AMD is characterized by a progressive retinal pigment epithelial (RPE) cell degeneration, mainly caused by an impaired antioxidative defense. One of the AMD therapeutic procedures involves injecting healthy RPE cells into the subretinal space, necessitating pure, healthy RPE cell suspensions. This study aims to electrically characterize RPE cells to demonstrate a possibility using simulations to separate healthy RPE cells from a mixture of healthy/oxidized cells by dielectrophoresis. Methods BPEI-1 rat RPE cells were exposed to hydrogen peroxide to create an in-vitro AMD cellular model. Cell viability was evaluated using various methods, including microscopic imaging, impedance-based real-time cell analysis, and the MTS assay. Healthy and oxidized cells were characterized by recording their dielectrophoretic spectra, and electric cell parameters (crossover frequency, membrane conductivity and permittivity, and cytoplasm conductivity) were computed. A COMSOL simulation was performed on a theoretical microfluidic-based dielectrophoretic separation chip using these parameters. Results Increasing the hydrogen peroxide concentration shifted the first crossover frequency toward lower values, and the cell membrane permittivity progressively increased. These changes were attributed to progressive membrane peroxidation, as they were diminished when measured on cells treated with the antioxidant N-acetylcysteine. The changes in the crossover frequency were sufficient for the efficient separation of healthy cells, as demonstrated by simulations. Conclusions The study demonstrates that dielectrophoresis can be used to separate healthy RPE cells from oxidized ones based on their electrical properties. This method could be a viable approach for obtaining pure, healthy RPE cell suspensions for AMD therapeutic procedures. Supplementary Information The online version contains supplementary material available at 10.1186/s12886-024-03617-0.

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A treatment within sight: challenges in the development of stem cell-derived photoreceptor therapies for retinal degenerative diseases

Cited by 2 publications

References 248 publications

Dielectrophoretic characterization of peroxidized retinal pigment epithelial cells as a model of age-related macular degeneration

Dielectrophoretic characterization of peroxidized retinal pigment epithelial cells as a model of age-related macular degeneration

Dielectrophoretic characterization of peroxidized retinal pigment epithelial cells as a model of age-related macular degeneration

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