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

TitleReal-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes.
Publication TypeJournal Article
Year of Publication2015
AuthorsGamal W, Borooah S, Smith S, Underwood I, Srsen V, Chandran S, Bagnaninchi PO, Dhillon B
JournalBiosens Bioelectron
Date Published2015 Sep 15
KeywordsBiological Assay, Cell Movement, Cells, Cultured, Computer Systems, Dielectric Spectroscopy, Equipment Design, Equipment Failure Analysis, Humans, Macular Degeneration, Microelectrodes, Reproducibility of Results, Retinal Pigment Epithelium, Sensitivity and Specificity, Tissue Array Analysis

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.

Alternate JournalBiosens Bioelectron
PubMed ID25950942
PubMed Central IDPMC4456427
Grant ListR42141 / / Wellcome Trust / United Kingdom
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