Molecular and cellular effects of in vitro shockwave treatment on lymphatic endothelial cells

PLoS One. 2014 Dec 11;9(12):e114806. doi: 10.1371/journal.pone.0114806. eCollection 2014.

Abstract

Extracorporeal shockwave treatment was shown to improve orthopaedic diseases and wound healing and to stimulate lymphangiogenesis in vivo. The aim of this study was to investigate in vitro shockwave treatment (IVSWT) effects on lymphatic endothelial cell (LEC) behavior and lymphangiogenesis. We analyzed migration, proliferation, vascular tube forming capability and marker expression changes of LECs after IVSWT compared with HUVECs. Finally, transcriptome- and miRNA analyses were conducted to gain deeper insight into the IVSWT-induced molecular mechanisms in LECs. The results indicate that IVSWT-mediated proliferation changes of LECs are highly energy flux density-dependent and LEC 2D as well as 3D migration was enhanced through IVSWT. IVSWT suppressed HUVEC 3D migration but enhanced vasculogenesis. Furthermore, we identified podoplaninhigh and podoplaninlow cell subpopulations, whose ratios changed upon IVSWT treatment. Transcriptome- and miRNA analyses on these populations showed differences in genes specific for signaling and vascular tissue. Our findings help to understand the cellular and molecular mechanisms underlying shockwave-induced lymphangiogenesis in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / radiation effects
  • Cell Proliferation / radiation effects
  • Endothelial Cells / pathology
  • Endothelial Cells / radiation effects*
  • Gene Expression Regulation
  • High-Energy Shock Waves*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lymphangiogenesis / genetics
  • Lymphangiogenesis / radiation effects*
  • Lymphatic Metastasis
  • Lymphatic Vessels / pathology
  • Lymphatic Vessels / radiation effects*
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • Signal Transduction / radiation effects
  • Transcriptome / genetics
  • Wound Healing / radiation effects

Substances

  • MicroRNAs

Grants and funding

This study was funded by: EU Biodesign Program (262948) (www.biodesign.eu) to HR and WH, a Femtech student fellowship from the Austrian research promotion agency FFG (www.ffg.at) to SR, the NewTissue Project (CFFG 818412) from the Austrian research promotion agency and City of Vienna (MA27 #06-06) and the City of Vienna Competence team reacTissue Project (MA27 #12-06) to DR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MH and SS are employed by TAmiRNA GmbH. TAmiRNA GmbH provided support in the form of salaries for authors MH and SS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.