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Lymphat Res Biol. 2017 Jun;15(2):130-135. doi: 10.1089/lrb.2016.0042. Epub 2017 May 9.

Lymphatic Endothelial Cells under Mechanical Stress: Altered Expression of Inflammatory Cytokines and Fibrosis.

Author information

1
1 Department of Plastic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.
2
2 Department of Orthopaedic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.

Abstract

BACKGROUND:

Secondary lymphedema, resulting from damage to lymphatic vessels, is a common sequela following surgical removal of lymph nodes for cancer. Current therapeutics for treating lymphedema are limited and further research on underlying causes is warranted. Published studies on molecular mechanisms of lymphedema primarily focus on lymphatic endothelial cells (LECs), which comprise the innermost lining of lymphatic capillaries and collecting vessels. However, traditional static culture of LECs may not adequately recapitulate the lymphedemous cell phenotype as transcriptomal comparison of human dermal LECs has shown significant differences in ex vivo and in vitro LEC gene expression. In this study, we designed a dynamic culture system, in which LECs were exposed to physiologic and excess mechanical strain to determine if native and lymphedemous phenotypes could be reproduced in vitro.

METHODS AND RESULTS:

Purified human LECs were cultured in silicon dishes and subjected to 0% (control), 4%, and 8% mechanical strain for 72 hours. Our results indicate that control and stretched LECs maintained a mature phenotype. Extreme stretching at 8% strain significantly increased LEC proliferation and significantly increased Prox1 expression, suggesting a lymphedemous cell phenotype resulting with lymphangiogenesis.

CONCLUSION:

Mechanical strain reinforced a mature lymphatic phenotype and excess strain promoted lymphangiogenesis, while altering collagen deposition and cytokine secretion.

KEYWORDS:

lymphangiogenesis; lymphatic endothelial cells; lymphedema; mechanical strain

PMID:
28486010
DOI:
10.1089/lrb.2016.0042
[Indexed for MEDLINE]

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