Details

Autor(en) / Beteiligte

• Gamal, W.
• Borooah, S.
• Smith, S.
• Underwood, I.
• Srsen, V.
• Chandran, S.
• Bagnaninchi, P.O.
• Dhillon, B.

Titel

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

Ist Teil von

• Biosensors & bioelectronics, 2015-09, Vol.71, p.445-455

Ort / Verlag

England: Elsevier B.V

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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±0.46μm/h) and control cell lines (10.69±0.21μm/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±0.28Ω1/2cm for the case cell line and 6.5±0.15Ω1/2cm 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. •hiPSC-RPE model was established and characterised on ECIS microelectrode arrays.•A reproducible electrical wound healing assay was used to mimic RPE cell damage.•Significant differences in migration rates were found between case and control.•Cells recovered through mesenchymal migration mirrored by impedance fluctuations.•Case cell line showed significantly higher adhesion than the control cell line.