Avraham T, Clavin NW, Daluvoy SV, Fernandez J, Soares MA, Cordeiro AP, Mehrara BJ, et al.
Plastic and reconstructive surgery. Date of publication 2009 Aug 1;volume 124(2):438-50.
1. Plast Reconstr Surg. 2009 Aug;124(2):438-50. doi: 10.1097/PRS.0b013e3181adcf4b.
Fibrosis is a key inhibitor of lymphatic regeneration.
Avraham T(1), Clavin NW, Daluvoy SV, Fernandez J, Soares MA, Cordeiro AP, Mehrara
BJ.
Author information:
(1)Division of Plastic and Reconstructive Surgery, Department of Surgery,
Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
BACKGROUND: Lymphedema is a common debilitating sequela of lymph node dissection.
Although numerous clinical studies suggest that factors that lead to fibrosis are
associated with the development of lymphedema, this relationship has not been
proven. The purpose of these experiments was therefore to evaluate lymphatic
regeneration in the setting of variable soft-tissue fibrosis.
METHODS: A section of mouse tail skin including the capillary and collecting
lymphatics was excised. Experimental animals (n = 20) were treated with topical
collagen type I gel and a moist dressing, whereas control animals (n = 20)
underwent excision followed by moist dressing alone. Fibrosis, acute lymphedema,
lymphatic function, gene expression, lymphatic endothelial cell proliferation,
and lymphatic fibrosis were evaluated at various time points.
RESULTS: Collagen gel treatment significantly decreased fibrosis, with an
attendant decrease in acute lymphedema and improved lymphatic function. Tails
treated with collagen gel demonstrated greater numbers of lymphatic vessels, more
normal lymphatic architecture, and more proliferating lymphatic endothelial
cells. These findings appeared to be independent of vascular endothelial growth
factor C expression. Decreased fibrosis was associated with a significant
decrease in the expression of extracellular matrix components. Finally, decreased
soft-tissue fibrosis was associated with a significant decrease in lymphatic
fibrosis as evidenced by the number of lymphatic endothelial cells that
coexpressed lymphatic and fibroblast markers.
CONCLUSIONS: Soft-tissue fibrosis is associated with impairment in lymphatic
regeneration and lymphatic function. These defects occur as a consequence of
impaired lymphatic endothelial cell proliferation, abnormal lymphatic
microarchitecture, and lymphatic fibrosis. Inhibition of fibrosis using a simple
topical dressing can markedly accelerate lymphatic repair and promote
regeneration of normal capillary lymphatics.
DOI: 10.1097/PRS.0b013e3181adcf4b
PMID: 19644258 [Indexed for MEDLINE]
