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Enhanced Human-Induced Pluripotent Stem Cell Derived Cardiomyocyte Maturation Using a Dual Microgradient Substrate.

E Huethorst1, M Hortigon2, V Zamora-Rodriguez2

  • 1Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom; Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, United Kingdom.

ACS Biomaterials Science & Engineering
|December 20, 2016
PubMed
Summary
This summary is machine-generated.

Topographical gradient substrates significantly enhance human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) maturation. Specific microgroove dimensions promote increased cell elongation and orientation, improving cardiac research potential.

Keywords:
biomaterialcardiac regenerationfunctionalityhiPSC-CMmicrogroovestopography

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Area of Science:

  • Biomedical Engineering
  • Stem Cell Biology
  • Cardiovascular Research

Background:

  • Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are valuable for cardiac research but possess an immature phenotype.
  • Immature hiPSC-CM characteristics can affect experimental outcomes and limit their utility.

Purpose of the Study:

  • To investigate the impact of topographical gradient substrates on hiPSC-CM morphology and function.
  • To determine if specific microgroove dimensions can promote hiPSC-CM maturation.

Main Methods:

  • Commercially available hiPSC-CM were cultured on substrates with varying microgroove dimensions (8-100 μm width, ~5 nm-1 μm depth).
  • Cellular morphology (eccentricity, elongation, orientation) and function (sarcomere length, contractility) were assessed at days 4 and 10.
  • Comparisons were made between cells on gradient substrates and a control flat substrate.

Main Results:

  • The deepest and widest microgroove regions (8-30 μm width, 0.85-1 μm depth) significantly increased hiPSC-CM eccentricity, elongation, and orientation compared to the control.
  • hiPSC-CM on these gradient regions exhibited a prolonged relaxation phase during contraction (400 ms vs. 200 ms).

Conclusions:

  • Dual microgradient substrates can effectively influence hiPSC-CM morphology and function.
  • These findings suggest that specific topographical cues can stimulate hiPSC-CM migration and maturation, advancing cardiac research applications.