Combinatorial polymer electrospun matrices promote physiologically-relevant cardiomyogenic stem cell differentiation

Myocardial infarction results in extensive cardiomyocyte death which can lead to fatal arrhythmias or congestive heart failure. Delivery of stem cells to repopulate damaged cardiac tissue may be an attractive and innovative solution for repairing the damaged heart. Instructive polymer scaffolds with...

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Bibliographic Details
Published in:PloS one 2011-12, Vol.6 (12), p.e28935-e28935
Main Authors: Gupta, Mukesh K, Walthall, Joel M, Venkataraman, Raghav, Crowder, Spencer W, Jung, Dae Kwang, Yu, Shann S, Feaster, Tromondae K, Wang, Xintong, Giorgio, Todd D, Hong, Charles C, Baudenbacher, Franz J, Hatzopoulos, Antonis K, Sung, Hak-Joon
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Base Sequence
Biodegradation
Biology
Biomedical engineering
Biomedical materials
Calcium (intracellular)
Calcium signalling
Caprolactone
Cardiomyocytes
Cell differentiation
Cell Differentiation - drug effects
Cell growth
Chain dynamics
Chemical properties
Chemistry
Combinatorial analysis
Congestive heart failure
Copolymerization
Copolymers
Damage
Developmental biology
Differentiation (biology)
DNA Primers
Electrospinning
Embryo cells
Embryonic stem cells
Embryos
Gene expression
Heart
Heart attack
Heart failure
Humans
Hydrophobicity
Immunohistochemistry
Intracellular
Intracellular signalling
Kinases
Magnetic Resonance Spectroscopy
Maintenance
Materials Science
Maturation
Mechanical properties
Medicine
Myocardial infarction
Myocardium - cytology
Myosin
Oxygen
Physicochemical properties
Polyethylene glycol
Polymer blends
Polymer industry
Polymers - pharmacology
Polyols
Reactive oxygen species
Reactive Oxygen Species - metabolism
Scaffolds
Stem cell transplantation
Stem cells
Stem Cells - cytology
Tissue engineering
Viability
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Summary:Myocardial infarction results in extensive cardiomyocyte death which can lead to fatal arrhythmias or congestive heart failure. Delivery of stem cells to repopulate damaged cardiac tissue may be an attractive and innovative solution for repairing the damaged heart. Instructive polymer scaffolds with a wide range of properties have been used extensively to direct the differentiation of stem cells. In this study, we have optimized the chemical and mechanical properties of an electrospun polymer mesh for directed differentiation of embryonic stem cells (ESCs) towards a cardiomyogenic lineage. A combinatorial polymer library was prepared by copolymerizing three distinct subunits at varying molar ratios to tune the physicochemical properties of the resulting polymer: hydrophilic polyethylene glycol (PEG), hydrophobic poly(ε-caprolactone) (PCL), and negatively-charged, carboxylated PCL (CPCL). Murine ESCs were cultured on electrospun polymeric scaffolds and their differentiation to cardiomyocytes was assessed through measurements of viability, intracellular reactive oxygen species (ROS), α-myosin heavy chain expression (α-MHC), and intracellular Ca(2+) signaling dynamics. Interestingly, ESCs on the most compliant substrate, 4%PEG-86%PCL-10%CPCL, exhibited the highest α-MHC expression as well as the most mature Ca(2+) signaling dynamics. To investigate the role of scaffold modulus in ESC differentiation, the scaffold fiber density was reduced by altering the electrospinning parameters. The reduced modulus was found to enhance α-MHC gene expression, and promote maturation of myocyte Ca(2+) handling. These data indicate that ESC-derived cardiomyocyte differentiation and maturation can be promoted by tuning the mechanical and chemical properties of polymer scaffold via copolymerization and electrospinning techniques.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0028935