Fibrosis Is a Key Inhibitor of Lymphatic Regeneration

被引:102
作者
Avraham, Tomer [1 ]
Clavin, Nicholas W. [1 ]
Daluvoy, Sanjay V. [1 ]
Fernandez, John [1 ]
Soares, Marc A. [1 ]
Cordeiro, Andrew P. [1 ]
Mehrara, Babak J. [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Div Plast & Reconstruct Surg, Dept Surg, New York, NY USA
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; BREAST-CANCER; NODE DISSECTION; WOUND REPAIR; LYMPHEDEMA; CELLS; BETA; TRANSDIFFERENTIATION; FIBROBLASTS; RADIATION;
D O I
10.1097/PRS.0b013e3181adcf4b
中图分类号
R61 [外科手术学];
学科分类号
摘要
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 micro-architecture, and lymphatic fibrosis. Inhibition of fibrosis using a simple topical dressing can markedly accelerate lymphatic repair and promote regeneration of normal capillary lymphatics. ( Plast. Reconstr. Surg. 124: 438, 2009.)
引用
收藏
页码:438 / 450
页数:13
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