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)
|
Text
130160.pdf - Published Version Available under License Creative Commons Attribution. 3MB |
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.
University Staff: Request a correction | Enlighten Editors: Update this record
Altmetric
Altmetric