Vascularized lymph node transplantation successfully reverses lymphedema and maintains immunity in a rat lymphedema model

Abstract Vascularized lymph node transplantation (VLNT) has shown inspiring results for the treatment of lymphedema. Nevertheless, it remains unclear how VLNT restores lymphatic drainage and whether or not immunity recovers after surgery. Hindlimb lymphedema model was created using rats with extensi...

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Main Authors: Ahmet Hamdi Sakarya, Chi‐Wei Huang, Chin‐Yu Yang, Hui‐Yi Hsiao, Frank Chun‐Shin Chang, Jung‐Ju Huang
Format: Article
Language:English
Published: Wiley 2022-09-01
Series:Bioengineering & Translational Medicine
Subjects:
Online Access:https://doi.org/10.1002/btm2.10301
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author Ahmet Hamdi Sakarya
Chi‐Wei Huang
Chin‐Yu Yang
Hui‐Yi Hsiao
Frank Chun‐Shin Chang
Jung‐Ju Huang
author_facet Ahmet Hamdi Sakarya
Chi‐Wei Huang
Chin‐Yu Yang
Hui‐Yi Hsiao
Frank Chun‐Shin Chang
Jung‐Ju Huang
author_sort Ahmet Hamdi Sakarya
collection DOAJ
description Abstract Vascularized lymph node transplantation (VLNT) has shown inspiring results for the treatment of lymphedema. Nevertheless, it remains unclear how VLNT restores lymphatic drainage and whether or not immunity recovers after surgery. Hindlimb lymphedema model was created using rats with extensive groin and popliteal lymph node removable following with radiotherapy, and the lymphedema was confirmed using indocyanine green (ICG) lymphangiography and micro‐computer tomography for volume measurement. VLNT was performed 1 month later. Volume measurement, ICG lymphangiography, histology, and immune reaction were done 1 month after surgery. VLNT successfully reduced the volume of the lymphedema hindlimb, restored lymphatic drainage function with proven lymphatic channel, and reduced lymphedema‐related inflammation and fibrosis. It promotes lymphangiogenesis shown from ICG lymphangiography, histology, and enhanced lymphangiogenesis gene expression. Dendritic cell trafficking via the regenerated lymphatic channels was successfully restored, and maintained systemic immune response was proved using dinitrofluorobenzene sensitization and challenge. VLNT effectively reduces lymphedema and promotes lymphatic regeneration in the capillary lymphatic but not the collecting lymphatic vessels. Along with the re‐established lymphatic system was the restoration of immune function locally and systemically. This correlated to clinical experience regarding the reduction of swelling and infection episodes after VLNT in lymphedema patients.
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spelling doaj.art-3f3d737fbc9e4c7c9a54a1c0afc078742022-12-22T03:20:17ZengWileyBioengineering & Translational Medicine2380-67612022-09-0173n/an/a10.1002/btm2.10301Vascularized lymph node transplantation successfully reverses lymphedema and maintains immunity in a rat lymphedema modelAhmet Hamdi Sakarya0Chi‐Wei Huang1Chin‐Yu Yang2Hui‐Yi Hsiao3Frank Chun‐Shin Chang4Jung‐Ju Huang5Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan TaiwanDivision of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan TaiwanDivision of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan TaiwanDivision of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan TaiwanCollege of Medicine Chang Gung University Taoyuan TaiwanDivision of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan TaiwanAbstract Vascularized lymph node transplantation (VLNT) has shown inspiring results for the treatment of lymphedema. Nevertheless, it remains unclear how VLNT restores lymphatic drainage and whether or not immunity recovers after surgery. Hindlimb lymphedema model was created using rats with extensive groin and popliteal lymph node removable following with radiotherapy, and the lymphedema was confirmed using indocyanine green (ICG) lymphangiography and micro‐computer tomography for volume measurement. VLNT was performed 1 month later. Volume measurement, ICG lymphangiography, histology, and immune reaction were done 1 month after surgery. VLNT successfully reduced the volume of the lymphedema hindlimb, restored lymphatic drainage function with proven lymphatic channel, and reduced lymphedema‐related inflammation and fibrosis. It promotes lymphangiogenesis shown from ICG lymphangiography, histology, and enhanced lymphangiogenesis gene expression. Dendritic cell trafficking via the regenerated lymphatic channels was successfully restored, and maintained systemic immune response was proved using dinitrofluorobenzene sensitization and challenge. VLNT effectively reduces lymphedema and promotes lymphatic regeneration in the capillary lymphatic but not the collecting lymphatic vessels. Along with the re‐established lymphatic system was the restoration of immune function locally and systemically. This correlated to clinical experience regarding the reduction of swelling and infection episodes after VLNT in lymphedema patients.https://doi.org/10.1002/btm2.10301immunitylymphedemarat lymphedema modelvascularized lymph node transfer
spellingShingle Ahmet Hamdi Sakarya
Chi‐Wei Huang
Chin‐Yu Yang
Hui‐Yi Hsiao
Frank Chun‐Shin Chang
Jung‐Ju Huang
Vascularized lymph node transplantation successfully reverses lymphedema and maintains immunity in a rat lymphedema model
Bioengineering & Translational Medicine
immunity
lymphedema
rat lymphedema model
vascularized lymph node transfer
title Vascularized lymph node transplantation successfully reverses lymphedema and maintains immunity in a rat lymphedema model
title_full Vascularized lymph node transplantation successfully reverses lymphedema and maintains immunity in a rat lymphedema model
title_fullStr Vascularized lymph node transplantation successfully reverses lymphedema and maintains immunity in a rat lymphedema model
title_full_unstemmed Vascularized lymph node transplantation successfully reverses lymphedema and maintains immunity in a rat lymphedema model
title_short Vascularized lymph node transplantation successfully reverses lymphedema and maintains immunity in a rat lymphedema model
title_sort vascularized lymph node transplantation successfully reverses lymphedema and maintains immunity in a rat lymphedema model
topic immunity
lymphedema
rat lymphedema model
vascularized lymph node transfer
url https://doi.org/10.1002/btm2.10301
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