title: Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation.
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.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA; Parker H. Petit Institute for Biotechnology and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Jingjia
authors.initials: J
authors.lastname: Han
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
authors.forename: Qingling
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Parker H. Petit Institute for Biotechnology and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Younan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Wagner
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA; Parker H. Petit Institute for Biotechnology and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA. Electronic address: chunhui.xu@emory.edu.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Xu
mesh_terms: D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D059008:Time-Lapse Imaging; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D002316:Cardiotonic Agents; D011091:Polyesters; C016240:polycaprolactone; D002118:Calcium
keywords: Cardiomyocyte; Electrospinning; Maturation; Scaffold; Stem cell