Direct visualisation of smooth muscle cell phenotypic plasticity and migration by long-term imaging

Research output: Contribution to journalConference Contribution

Abstract

An abnormal increase in the number and distribution of SMCs is a key feature of the vascular remodelling that underlies cardiovascular disease. The predominant explanation for these changes is that medial SMCs undergo phenotypic modulation followed by migration to the intima and subsequent proliferation. However, there has been no direct demonstration of this dedifferentiation process by tracking the fate of contractile SMCs and the very existence of phenotypic plasticity has been questioned. We therefore employed high-resolution, multi-wavelength fluorescence and simultaneous phase contrast, time-lapse microscopy to monitor the fate of unambiguously identified, freshly isolated, mature SMCs. Phenotypic modulation of the initially contractile SMCs was clearly observed in response to serum-containing culture media. Extensive cellular remodelling occurred, though a consistent sequence of events was observed in which spindle-shaped SMCs initially rounded up following exposure to media. The cells remained round for varying lengths of time (1-3 days) before spreading outwards and, at this stage, repetitive contractions occurred (measured via bursts of high speed imaging). Finally, the cells flattened further and migration began. Surprisingly, after the onset of migration, the extrusion of subcellular structures (e.g. mitochondria) from one cell and their subsequent uptake by another cell was observed. The phenotypically modulated SMCs also formed direct connections with other cells (tunnelling nanotubes). These results highlight the complexity of the remodelling process, the highly dynamic cellular interactions involved and the significant cell-cell variation in response and will enable a detailed picture of SMC remodelling to be built.
LanguageEnglish
Article number867.12
Number of pages1
JournalFASEB Journal
Volume28
Issue numberSuppl 1
Publication statusPublished - 30 Apr 2014
EventExperimental Biology - , United States
Duration: 26 Apr 201430 Apr 2014

Fingerprint

Smooth Muscle Myocytes
Cell Movement
Plasticity
Muscle
Visualization
Cells
Modulation
Imaging techniques
Mitochondria
Nanotubes
Extrusion
Culture Media
Microscopic examination
Demonstrations
Fluorescence
Wavelength
Cell Plasticity
Microscopy
Cardiovascular Diseases
Serum

Keywords

  • smooth muscle cell
  • phenotypic plasticity
  • time lapse microscopy

Cite this

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title = "Direct visualisation of smooth muscle cell phenotypic plasticity and migration by long-term imaging",
abstract = "An abnormal increase in the number and distribution of SMCs is a key feature of the vascular remodelling that underlies cardiovascular disease. The predominant explanation for these changes is that medial SMCs undergo phenotypic modulation followed by migration to the intima and subsequent proliferation. However, there has been no direct demonstration of this dedifferentiation process by tracking the fate of contractile SMCs and the very existence of phenotypic plasticity has been questioned. We therefore employed high-resolution, multi-wavelength fluorescence and simultaneous phase contrast, time-lapse microscopy to monitor the fate of unambiguously identified, freshly isolated, mature SMCs. Phenotypic modulation of the initially contractile SMCs was clearly observed in response to serum-containing culture media. Extensive cellular remodelling occurred, though a consistent sequence of events was observed in which spindle-shaped SMCs initially rounded up following exposure to media. The cells remained round for varying lengths of time (1-3 days) before spreading outwards and, at this stage, repetitive contractions occurred (measured via bursts of high speed imaging). Finally, the cells flattened further and migration began. Surprisingly, after the onset of migration, the extrusion of subcellular structures (e.g. mitochondria) from one cell and their subsequent uptake by another cell was observed. The phenotypically modulated SMCs also formed direct connections with other cells (tunnelling nanotubes). These results highlight the complexity of the remodelling process, the highly dynamic cellular interactions involved and the significant cell-cell variation in response and will enable a detailed picture of SMC remodelling to be built.",
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Direct visualisation of smooth muscle cell phenotypic plasticity and migration by long-term imaging. / Sandison, Mairi; Chalmers, Susan; Dempster, John; McCarron, John.

In: FASEB Journal, Vol. 28, No. Suppl 1, 867.12, 30.04.2014.

Research output: Contribution to journalConference Contribution

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AU - Sandison, Mairi

AU - Chalmers, Susan

AU - Dempster, John

AU - McCarron, John

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