Enhanced human-induced pluripotent stem cell derived cardiomyocyte maturation using a dual microgradient substrate

Huethorst, E., Hortigon, M. , Zamora-Rodriguez, V., Reynolds, P.M., Burton, F., Smith, G. and Gadegaard, N. (2016) Enhanced human-induced pluripotent stem cell derived cardiomyocyte maturation using a dual microgradient substrate. ACS Biomaterials Science and Engineering, 2(12), pp. 2231-2239. (doi:10.1021/acsbiomaterials.6b00426) (PMID:27990488) (PMCID:PMC5155309)

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Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) raise many possibilities for cardiac research but they exhibit an immature phenotype, which influences experimental outcomes. The aim of our research is to investigate the effects of a topographical gradient substrate on the morphology and function of commercially available hiPSC-CM. The lateral dimensions the microgrooves on the substrate varied from 8 to 100 μm space between the 8 μm grooves on one axis and from ~5 nm to ~1 μm in depth on the other axis. Cells were seeded homogeneously across the substrate and according to the manufacturers protocols. At day 4 and 10, measures of eccentricity, elongation, orientation, sarcomere length (SL) and contractility of the hiPSC-CM were taken. Only in the deepest and widest region (8-30 μm wide and 0.85-1 μm deep) showed a significantly higher percentage of hiPSC-CM with an increased eccentricity (31.3±6.4%), elongation (10.4±4.3%) and orientation (<10°)(32.1±2.7%) when compared with the control (flat substrate)(15.8±5.0%, 3.4±2.7% and 10.6±1.1%, respectively). Additionally, during stimulus-induced contraction the relaxation phase of the twitch was prolonged (400 ms), compared to non-elongated cells (200 ms). These findings support the potential use of dual micro-gradient substrates to investigate substrate topographies that stimulate migration and/or maturation of hiPSC-CM.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Burton, Dr Francis and Zamora Rodriguez, Dr Victor and Smith, Professor Godfrey and Gadegaard, Professor Nikolaj and Huethorst, Miss Eline and Reynolds, Mr Paul and Hortigon, Dr Maria
Authors: Huethorst, E., Hortigon, M., Zamora-Rodriguez, V., Reynolds, P.M., Burton, F., Smith, G., and Gadegaard, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Science and Engineering > School of Engineering
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:ACS Biomaterials Science and Engineering
Publisher:American Chemical Society
ISSN:2373-9878
ISSN (Online):2373-9878
Published Online:17 October 2016
Copyright Holders:Copyright © 2016 American Chemical Society
First Published:First published in ACS Biomaterials Science and Engineering 2(12):2231-2239
Publisher Policy:Reproduced under a creative commons license
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
600931Development of nanopatterned substrates for the delivery of high quality stem cellsNikolaj GadegaardBiotechnology and Biological Sciences Research Council (BBSRC)BB/K011235/1ENG - BIOMEDICAL ENGINEERING