Mechanisms of lymphatic regeneration after tissue transfer.

Lymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies...

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Main Authors: Alan Yan, Tomer Avraham, Jamie C Zampell, Seth Z Aschen, Babak J Mehrara
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-02-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3040774?pdf=render
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spelling doaj-376ffd6546d74f119ddd87b395a354742020-11-25T00:48:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-02-0162e1720110.1371/journal.pone.0017201Mechanisms of lymphatic regeneration after tissue transfer.Alan YanTomer AvrahamJamie C ZampellSeth Z AschenBabak J MehraraLymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies was to investigate the mechanisms that regulate lymphatic regeneration after tissue transfer.Nude mice (recipients) underwent 2-mm tail skin excisions that were either left open or repaired with full-thickness skin grafts harvested from donor transgenic mice that expressed green fluorescent protein in all tissues or from LYVE-1 knockout mice. Lymphatic regeneration, expression of VEGF-C, macrophage infiltration, and potential for skin grafting to bypass damaged lymphatics were assessed.Skin grafts healed rapidly and restored lymphatic flow. Lymphatic regeneration occurred beginning at the peripheral edges of the graft, primarily from ingrowth of new lymphatic vessels originating from the recipient mouse. In addition, donor lymphatic vessels appeared to spontaneously re-anastomose with recipient vessels. Patterns of VEGF-C expression and macrophage infiltration were temporally and spatially associated with lymphatic regeneration. When compared to mice treated with excision only, there was a 4-fold decrease in tail volumes, 2.5-fold increase in lymphatic transport by lymphoscintigraphy, 40% decrease in dermal thickness, and 54% decrease in scar index in skin-grafted animals, indicating that tissue transfer could bypass damaged lymphatics and promote rapid lymphatic regeneration.Our studies suggest that lymphatic regeneration after tissue transfer occurs by ingrowth of lymphatic vessels and spontaneous re-connection of existing lymphatics. This process is temporally and spatially associated with VEGF-C expression and macrophage infiltration. Finally, tissue transfer can be used to bypass damaged lymphatics and promote rapid lymphatic regeneration.http://europepmc.org/articles/PMC3040774?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Alan Yan
Tomer Avraham
Jamie C Zampell
Seth Z Aschen
Babak J Mehrara
spellingShingle Alan Yan
Tomer Avraham
Jamie C Zampell
Seth Z Aschen
Babak J Mehrara
Mechanisms of lymphatic regeneration after tissue transfer.
PLoS ONE
author_facet Alan Yan
Tomer Avraham
Jamie C Zampell
Seth Z Aschen
Babak J Mehrara
author_sort Alan Yan
title Mechanisms of lymphatic regeneration after tissue transfer.
title_short Mechanisms of lymphatic regeneration after tissue transfer.
title_full Mechanisms of lymphatic regeneration after tissue transfer.
title_fullStr Mechanisms of lymphatic regeneration after tissue transfer.
title_full_unstemmed Mechanisms of lymphatic regeneration after tissue transfer.
title_sort mechanisms of lymphatic regeneration after tissue transfer.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-02-01
description Lymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies was to investigate the mechanisms that regulate lymphatic regeneration after tissue transfer.Nude mice (recipients) underwent 2-mm tail skin excisions that were either left open or repaired with full-thickness skin grafts harvested from donor transgenic mice that expressed green fluorescent protein in all tissues or from LYVE-1 knockout mice. Lymphatic regeneration, expression of VEGF-C, macrophage infiltration, and potential for skin grafting to bypass damaged lymphatics were assessed.Skin grafts healed rapidly and restored lymphatic flow. Lymphatic regeneration occurred beginning at the peripheral edges of the graft, primarily from ingrowth of new lymphatic vessels originating from the recipient mouse. In addition, donor lymphatic vessels appeared to spontaneously re-anastomose with recipient vessels. Patterns of VEGF-C expression and macrophage infiltration were temporally and spatially associated with lymphatic regeneration. When compared to mice treated with excision only, there was a 4-fold decrease in tail volumes, 2.5-fold increase in lymphatic transport by lymphoscintigraphy, 40% decrease in dermal thickness, and 54% decrease in scar index in skin-grafted animals, indicating that tissue transfer could bypass damaged lymphatics and promote rapid lymphatic regeneration.Our studies suggest that lymphatic regeneration after tissue transfer occurs by ingrowth of lymphatic vessels and spontaneous re-connection of existing lymphatics. This process is temporally and spatially associated with VEGF-C expression and macrophage infiltration. Finally, tissue transfer can be used to bypass damaged lymphatics and promote rapid lymphatic regeneration.
url http://europepmc.org/articles/PMC3040774?pdf=render
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