Human airway smooth muscle maintain in situ cell orientation and phenotype when cultured on aligned electrospun scaffolds
Human airway smooth muscle (HASM) contraction plays a central role in regulating airway resistance in both healthy and asthmatic bronchioles. In vitro studies that investigate the intricate mechanisms that regulate this contractile process are predominantly conducted on tissue culture plastic, a rig...
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| Vydáno v: | American journal of physiology. Lung cellular and molecular physiology Ročník 307; číslo 1; s. L38 |
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| Hlavní autoři: | , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
01.07.2014
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| ISSN: | 1522-1504, 1522-1504 |
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| Abstract | Human airway smooth muscle (HASM) contraction plays a central role in regulating airway resistance in both healthy and asthmatic bronchioles. In vitro studies that investigate the intricate mechanisms that regulate this contractile process are predominantly conducted on tissue culture plastic, a rigid, 2D geometry, unlike the 3D microenvironment smooth muscle cells are exposed to in situ. It is increasingly apparent that cellular characteristics and responses are altered between cells cultured on 2D substrates compared with 3D topographies. Electrospinning is an attractive method to produce 3D topographies for cell culturing as the fibers produced have dimensions within the nanometer range, similar to cells' natural environment. We have developed an electrospun scaffold using the nondegradable, nontoxic, polymer polyethylene terephthalate (PET) composed of uniaxially orientated nanofibers and have evaluated this topography's effect on HASM cell adhesion, alignment, and morphology. The fibers orientation provided contact guidance enabling the formation of fully aligned sheets of smooth muscle. Moreover, smooth muscle cells cultured on the scaffold present an elongated cell phenotype with altered contractile protein levels and distribution. HASM cells cultured on this scaffold responded to the bronchoconstrictor bradykinin. The platform presented provides a novel in vitro model that promotes airway smooth muscle cell development toward a more in vivo-like phenotype while providing topological cues to ensure full cell alignment. |
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| AbstractList | Human airway smooth muscle (HASM) contraction plays a central role in regulating airway resistance in both healthy and asthmatic bronchioles. In vitro studies that investigate the intricate mechanisms that regulate this contractile process are predominantly conducted on tissue culture plastic, a rigid, 2D geometry, unlike the 3D microenvironment smooth muscle cells are exposed to in situ. It is increasingly apparent that cellular characteristics and responses are altered between cells cultured on 2D substrates compared with 3D topographies. Electrospinning is an attractive method to produce 3D topographies for cell culturing as the fibers produced have dimensions within the nanometer range, similar to cells' natural environment. We have developed an electrospun scaffold using the nondegradable, nontoxic, polymer polyethylene terephthalate (PET) composed of uniaxially orientated nanofibers and have evaluated this topography's effect on HASM cell adhesion, alignment, and morphology. The fibers orientation provided contact guidance enabling the formation of fully aligned sheets of smooth muscle. Moreover, smooth muscle cells cultured on the scaffold present an elongated cell phenotype with altered contractile protein levels and distribution. HASM cells cultured on this scaffold responded to the bronchoconstrictor bradykinin. The platform presented provides a novel in vitro model that promotes airway smooth muscle cell development toward a more in vivo-like phenotype while providing topological cues to ensure full cell alignment. Human airway smooth muscle (HASM) contraction plays a central role in regulating airway resistance in both healthy and asthmatic bronchioles. In vitro studies that investigate the intricate mechanisms that regulate this contractile process are predominantly conducted on tissue culture plastic, a rigid, 2D geometry, unlike the 3D microenvironment smooth muscle cells are exposed to in situ. It is increasingly apparent that cellular characteristics and responses are altered between cells cultured on 2D substrates compared with 3D topographies. Electrospinning is an attractive method to produce 3D topographies for cell culturing as the fibers produced have dimensions within the nanometer range, similar to cells' natural environment. We have developed an electrospun scaffold using the nondegradable, nontoxic, polymer polyethylene terephthalate (PET) composed of uniaxially orientated nanofibers and have evaluated this topography's effect on HASM cell adhesion, alignment, and morphology. The fibers orientation provided contact guidance enabling the formation of fully aligned sheets of smooth muscle. Moreover, smooth muscle cells cultured on the scaffold present an elongated cell phenotype with altered contractile protein levels and distribution. HASM cells cultured on this scaffold responded to the bronchoconstrictor bradykinin. The platform presented provides a novel in vitro model that promotes airway smooth muscle cell development toward a more in vivo-like phenotype while providing topological cues to ensure full cell alignment.Human airway smooth muscle (HASM) contraction plays a central role in regulating airway resistance in both healthy and asthmatic bronchioles. In vitro studies that investigate the intricate mechanisms that regulate this contractile process are predominantly conducted on tissue culture plastic, a rigid, 2D geometry, unlike the 3D microenvironment smooth muscle cells are exposed to in situ. It is increasingly apparent that cellular characteristics and responses are altered between cells cultured on 2D substrates compared with 3D topographies. Electrospinning is an attractive method to produce 3D topographies for cell culturing as the fibers produced have dimensions within the nanometer range, similar to cells' natural environment. We have developed an electrospun scaffold using the nondegradable, nontoxic, polymer polyethylene terephthalate (PET) composed of uniaxially orientated nanofibers and have evaluated this topography's effect on HASM cell adhesion, alignment, and morphology. The fibers orientation provided contact guidance enabling the formation of fully aligned sheets of smooth muscle. Moreover, smooth muscle cells cultured on the scaffold present an elongated cell phenotype with altered contractile protein levels and distribution. HASM cells cultured on this scaffold responded to the bronchoconstrictor bradykinin. The platform presented provides a novel in vitro model that promotes airway smooth muscle cell development toward a more in vivo-like phenotype while providing topological cues to ensure full cell alignment. |
| Author | Lewis, M P Morris, G E Brightling, C E Bridge, J C Ghaemmaghami, A M Knox, A J Eltboli, O M I Aylott, J W Rose, F R A J |
| Author_xml | – sequence: 1 givenname: G E surname: Morris fullname: Morris, G E organization: Division of Drug Delivery and Tissue Engineering, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom – sequence: 2 givenname: J C surname: Bridge fullname: Bridge, J C organization: Division of Drug Delivery and Tissue Engineering, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom – sequence: 3 givenname: O M I surname: Eltboli fullname: Eltboli, O M I organization: NIHR Respiratory Biomedical Research Unit, University of Leicester, Leicester, United Kingdom – sequence: 4 givenname: M P surname: Lewis fullname: Lewis, M P – sequence: 5 givenname: A J surname: Knox fullname: Knox, A J organization: Division of Respiratory Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom – sequence: 6 givenname: J W surname: Aylott fullname: Aylott, J W organization: Laboratory of Biophysics and Surface Analysis, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom; and – sequence: 7 givenname: C E surname: Brightling fullname: Brightling, C E organization: NIHR Respiratory Biomedical Research Unit, University of Leicester, Leicester, United Kingdom – sequence: 8 givenname: A M surname: Ghaemmaghami fullname: Ghaemmaghami, A M organization: Division of Immunology, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom – sequence: 9 givenname: F R A J surname: Rose fullname: Rose, F R A J email: felicity.rose@nottingham.ac.uk organization: Division of Drug Delivery and Tissue Engineering, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom; felicity.rose@nottingham.ac.uk |
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| References | 25833917 - Am J Physiol Lung Cell Mol Physiol. 2015 Apr 1;308(7):L729. doi: 10.1152/ajplung.zh5-6728-corr.2015. |
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| SubjectTerms | Biocompatible Materials - pharmacology Cell Adhesion - drug effects Cell Adhesion - physiology Cell Culture Techniques Cell Proliferation Cells, Cultured Cellular Microenvironment Humans Lung - cytology Models, Biological Muscle, Smooth - cytology Myocytes, Smooth Muscle - cytology Nanofibers Polyethylene Terephthalates - pharmacology Tissue Engineering - methods Tissue Scaffolds |
| Title | Human airway smooth muscle maintain in situ cell orientation and phenotype when cultured on aligned electrospun scaffolds |
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