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Author Notes:

Corresponding author at: Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA. Email: chunhui.xu@emory.edu

J.H. conceived and designed the study, performed experiments, analyzed and interpreted the data, and wrote the manuscript. Q.W. performed experiments and analyzed the data, and reviewed the manuscript.

Y.X. provided guidance, experimental reagents, and instruments for the preparation of electrospun fibers, and revised the manuscript. M.B.W. provided guidance, experimental reagents, equipment, and analytical tools for the MEA recording and calcium imaging, and revised the manuscript. C.X. conceived and oversaw the study, and revised the manuscript.

We thank Dr. Wenying Liu for her help with the initial setup of the electrospinning and Mr. Xiyu Li for his assistance with SEM.

We also thank Emory Children's Pediatric Research Center Flow Cytometry Core and Animal Physiology Core, which are supported by Children's Healthcare of Atlanta. Q.W. was supported by the Center for Pediatric Nanomedicine at Emory/Georgia Tech.

The authors declare that there is no conflict of interests.

Subjects:

Research Funding:

This project was supported in part by the NIH grants R21HL118454 and R21HL123928 to C.X.

Keywords:

  • Cardiomyocyte
  • Electrospinning
  • Maturation
  • Scaffold
  • Stem cell

Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation

Tools:

Journal Title:

Stem Cell Research

Volume:

Volume 16, Number 3

Publisher:

, Pages 740-750

Type of Work:

Article | Final Publisher PDF

Abstract:

Enhancing the maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) will facilitate their applications in disease modeling and drug discovery. Previous studies suggest that cell alignment could enhance hPSC-CM maturation; however, the robustness of this approach has not been well investigated. To this end, we examined if the anisotropic orientation of hPSC-CMs imposed by the underlying aligned fibers within a 3D microenvironment could improve the maturation of hPSC-CMs. Enriched hPSC-CMs were cultured for two weeks on Matrigel-coated anisotropic (aligned) and isotropic (random) polycaprolactone (PCL) fibrous scaffolds, as well as tissue culture polystyrenes (TCPs) as a control. As expected, hPSC-CMs grown on the two types of fibrous scaffolds exhibited anisotropic and isotropic orientations, respectively. Similar to cells on TCPs, hPSC-CMs cultured on these scaffolds expressed CM-associated proteins and were pharmacologically responsive to adrenergic receptor agonists, a muscarinic agonist, and a gap junction uncoupler in a dose-dependent manner. Although hPSC-CMs grown on anisotropic fibrous scaffolds displayed the highest expression of genes encoding a number of sarcomere proteins, calcium handling proteins and ion channels, their calcium transient kinetics were slower than cells grown on TCPs. These results suggest that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs.

Copyright information:

© 2016 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nd/4.0/).

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