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Real-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. Humanized disease models are required to develop new therapies for currently incurable forms of AMD. In this work, a tissue-on-a-chip approach was developed through combining human induced pluripotent st...

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Autores principales: Gamal, W., Borooah, S., Smith, S., Underwood, I., Srsen, V., Chandran, S., Bagnaninchi, P.O., Dhillon, B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Advanced Technology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456427/
https://www.ncbi.nlm.nih.gov/pubmed/25950942
http://dx.doi.org/10.1016/j.bios.2015.04.079
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author Gamal, W.
Borooah, S.
Smith, S.
Underwood, I.
Srsen, V.
Chandran, S.
Bagnaninchi, P.O.
Dhillon, B.
author_facet Gamal, W.
Borooah, S.
Smith, S.
Underwood, I.
Srsen, V.
Chandran, S.
Bagnaninchi, P.O.
Dhillon, B.
author_sort Gamal, W.
collection PubMed
description Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. Humanized disease models are required to develop new therapies for currently incurable forms of AMD. In this work, a tissue-on-a-chip approach was developed through combining human induced pluripotent stem cells, Electric Cell–substrate Impedance Sensing (ECIS) and reproducible electrical wounding assays to model and quantitatively study AMD. Retinal Pigment Epithelium (RPE) cells generated from a patient with an inherited macular degeneration and from an unaffected sibling were used to test the model platform on which a reproducible electrical wounding assay was conducted to model RPE damage. First, a robust and reproducible real-time quantitative monitoring over a 25-day period demonstrated the establishment and maturation of RPE layers on the microelectrode arrays. A spatially controlled RPE layer damage that mimicked cell loss in AMD disease was then initiated. Post recovery, significant differences (P<0.01) in migration rates were found between case (8.6±0.46 μm/h) and control cell lines (10.69±0.21 μm/h). Quantitative data analysis suggested this was achieved due to lower cell–substrate adhesion in the control cell line. The ECIS cell–substrate adhesion parameter (α) was found to be 7.8±0.28 Ω(1/2) cm for the case cell line and 6.5±0.15 Ω(1/2) cm for the control. These findings were confirmed using cell adhesion biochemical assays. The developed disease model-on-a-chip is a powerful platform for translational studies with considerable potential to investigate novel therapies by enabling real-time, quantitative and reproducible patient-specific RPE cell repair studies.
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spelling pubmed-44564272015-09-15 Real-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes Gamal, W. Borooah, S. Smith, S. Underwood, I. Srsen, V. Chandran, S. Bagnaninchi, P.O. Dhillon, B. Biosens Bioelectron Article Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. Humanized disease models are required to develop new therapies for currently incurable forms of AMD. In this work, a tissue-on-a-chip approach was developed through combining human induced pluripotent stem cells, Electric Cell–substrate Impedance Sensing (ECIS) and reproducible electrical wounding assays to model and quantitatively study AMD. Retinal Pigment Epithelium (RPE) cells generated from a patient with an inherited macular degeneration and from an unaffected sibling were used to test the model platform on which a reproducible electrical wounding assay was conducted to model RPE damage. First, a robust and reproducible real-time quantitative monitoring over a 25-day period demonstrated the establishment and maturation of RPE layers on the microelectrode arrays. A spatially controlled RPE layer damage that mimicked cell loss in AMD disease was then initiated. Post recovery, significant differences (P<0.01) in migration rates were found between case (8.6±0.46 μm/h) and control cell lines (10.69±0.21 μm/h). Quantitative data analysis suggested this was achieved due to lower cell–substrate adhesion in the control cell line. The ECIS cell–substrate adhesion parameter (α) was found to be 7.8±0.28 Ω(1/2) cm for the case cell line and 6.5±0.15 Ω(1/2) cm for the control. These findings were confirmed using cell adhesion biochemical assays. The developed disease model-on-a-chip is a powerful platform for translational studies with considerable potential to investigate novel therapies by enabling real-time, quantitative and reproducible patient-specific RPE cell repair studies. Elsevier Advanced Technology 2015-09-15 /pmc/articles/PMC4456427/ /pubmed/25950942 http://dx.doi.org/10.1016/j.bios.2015.04.079 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gamal, W.
Borooah, S.
Smith, S.
Underwood, I.
Srsen, V.
Chandran, S.
Bagnaninchi, P.O.
Dhillon, B.
Real-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes
title Real-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes
title_full Real-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes
title_fullStr Real-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes
title_full_unstemmed Real-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes
title_short Real-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes
title_sort real-time quantitative monitoring of hipsc-based model of macular degeneration on electric cell-substrate impedance sensing microelectrodes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456427/
https://www.ncbi.nlm.nih.gov/pubmed/25950942
http://dx.doi.org/10.1016/j.bios.2015.04.079
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