title: Polymer microfiber meshes facilitate cardiac differentiation of c-kit(+) human cardiac stem cells.
abstract: Electrospun microfiber meshes have been shown to support the proliferation and differentiation of many types of stem cells, but the phenotypic fate of c-kit(+) human cardiac stem cells (hCSCs) have not been explored. To this end, we utilized thin (~5µm) elastomeric meshes consisting of aligned 1.7µm diameter poly (ester-urethane urea) microfibers as substrates to examine their effect on hCSC viability, morphology, proliferation, and differentiation relative to cells cultured on tissue culture polystyrene (TCPS). The results showed that cells on microfiber meshes displayed an elongated morphology aligned in the direction of fiber orientation, lower proliferation rates, but increased expressions of genes and proteins majorly associated with cardiomyocyte phenotype. The early (NK2 homeobox 5, Nkx2.5) and late (cardiac troponin I, cTnI) cardiomyocyte genes were significantly increased on meshes (Nkx=2.5 56.2±13.0, cTnl=2.9±0.56,) over TCPS (Nkx2.5=4.2±0.9, cTnl=1.6±0.5, n=9, p<0.05 for both groups) after differentiation. In contrast, expressions of smooth muscle markers, Gata6 and myosin heavy chain (SM-MHC), were decreased on meshes. Immunocytochemical analysis with cardiac antibody exhibited the similar pattern of above cardiac differentiation. We conclude that aligned microfiber meshes are suitable for guiding cardiac differentiation of hCSCs and may facilitate stem cell-based therapies for treatment of cardiac diseases.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Kan
authors.affiliation: Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Thayer
authors.affiliation: Research Institute of Heart Failure, Shanghai East Hospital of Tongji University, Shanghai, PR China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ledford
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA, United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: Goldstein
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA, United States.
authors.forename: Guohua
authors.initials: G
authors.lastname: Cao
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States. Electronic address: jiahe@vt.edu.
authors.forename: Jia-Qiang
authors.initials: JQ
authors.lastname: He
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D009206:Myocardium / Q000166:cytology*; D011091:Polyesters / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D011091:Polyesters; C497893:poly(ester urethane)urea; D019009:Proto-Oncogene Proteins c-kit
keywords: Cardiac patch; Differentiation; Microfiber mesh; Poly (ester-urethane urea); Proliferation; c-kithuman cardiac stem cell