Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model

Chronic lymphedema after cancer treatment is common and there is still no cure for this disease. We herein investigated the lymphangiogenic capacity of adipose tissue-derived microvascular fragments (MVF), which contain stem cells and lymphatic vessel fragments. Secondary lymphedema was induced in t...

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Main Authors: Florian S Frueh, Laura Gassert, Claudia Scheuer, Andreas Müller, Peter Fries, Anne S Boewe, Emmanuel Ampofo, Claudia E Rübe, Michael D Menger, Matthias W Laschke
Format: Article
Language:English
Published: SAGE Publishing 2022-07-01
Series:Journal of Tissue Engineering
Online Access:https://doi.org/10.1177/20417314221109957
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author Florian S Frueh
Laura Gassert
Claudia Scheuer
Andreas Müller
Peter Fries
Anne S Boewe
Emmanuel Ampofo
Claudia E Rübe
Michael D Menger
Matthias W Laschke
author_facet Florian S Frueh
Laura Gassert
Claudia Scheuer
Andreas Müller
Peter Fries
Anne S Boewe
Emmanuel Ampofo
Claudia E Rübe
Michael D Menger
Matthias W Laschke
author_sort Florian S Frueh
collection DOAJ
description Chronic lymphedema after cancer treatment is common and there is still no cure for this disease. We herein investigated the lymphangiogenic capacity of adipose tissue-derived microvascular fragments (MVF), which contain stem cells and lymphatic vessel fragments. Secondary lymphedema was induced in the hindlimbs of C57BL/6J mice. Green fluorescence protein (GFP) + MVF were isolated from transgenic C57BL/6Tg (CAG-EGFP)1Osb/J mice, suspended in collagen hydrogel, and injected in the lymphadenectomy defect of wild-type animals. This crossover model allowed the detection of MVF-derived blood and lymphatic vessels after transplantation. The MVF group was compared with animals receiving collagen hydrogel only or a sham intervention. Lymphangiogenic effects were analyzed using volumetry, magnetic resonance (MR) lymphography, histology, and immunohistochemistry. MVF injection resulted in reduced hindlimb volumes when compared to non-treated controls. MR lymphography revealed lymphatic regeneration with reduced dermal backflow after MVF treatment. Finally, MVF transplantation promoted popliteal angiogenesis and lymphangiogenesis associated with a significantly increased microvessel and lymphatic vessel density. These findings indicate that MVF transplantation represents a promising approach to induce therapeutic lymphangiogenesis.
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spelling doaj.art-f5e23f791ef747c9b6bbf2e3aef033192022-12-22T02:07:46ZengSAGE PublishingJournal of Tissue Engineering2041-73142022-07-011310.1177/20417314221109957Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema modelFlorian S Frueh0Laura Gassert1Claudia Scheuer2Andreas Müller3Peter Fries4Anne S Boewe5Emmanuel Ampofo6Claudia E Rübe7Michael D Menger8Matthias W Laschke9Institute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, GermanyInstitute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, GermanyInstitute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, GermanyClinic of Diagnostic and Interventional Radiology, Saarland University Medical Center, Homburg/Saar, GermanyClinic of Diagnostic and Interventional Radiology, Saarland University Medical Center, Homburg/Saar, GermanyInstitute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, GermanyInstitute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, GermanyDepartment of Radiotherapy and Radiation Oncology, Saarland University Medical Centre, Homburg/Saar, GermanyInstitute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, GermanyInstitute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, GermanyChronic lymphedema after cancer treatment is common and there is still no cure for this disease. We herein investigated the lymphangiogenic capacity of adipose tissue-derived microvascular fragments (MVF), which contain stem cells and lymphatic vessel fragments. Secondary lymphedema was induced in the hindlimbs of C57BL/6J mice. Green fluorescence protein (GFP) + MVF were isolated from transgenic C57BL/6Tg (CAG-EGFP)1Osb/J mice, suspended in collagen hydrogel, and injected in the lymphadenectomy defect of wild-type animals. This crossover model allowed the detection of MVF-derived blood and lymphatic vessels after transplantation. The MVF group was compared with animals receiving collagen hydrogel only or a sham intervention. Lymphangiogenic effects were analyzed using volumetry, magnetic resonance (MR) lymphography, histology, and immunohistochemistry. MVF injection resulted in reduced hindlimb volumes when compared to non-treated controls. MR lymphography revealed lymphatic regeneration with reduced dermal backflow after MVF treatment. Finally, MVF transplantation promoted popliteal angiogenesis and lymphangiogenesis associated with a significantly increased microvessel and lymphatic vessel density. These findings indicate that MVF transplantation represents a promising approach to induce therapeutic lymphangiogenesis.https://doi.org/10.1177/20417314221109957
spellingShingle Florian S Frueh
Laura Gassert
Claudia Scheuer
Andreas Müller
Peter Fries
Anne S Boewe
Emmanuel Ampofo
Claudia E Rübe
Michael D Menger
Matthias W Laschke
Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model
Journal of Tissue Engineering
title Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model
title_full Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model
title_fullStr Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model
title_full_unstemmed Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model
title_short Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model
title_sort adipose tissue derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model
url https://doi.org/10.1177/20417314221109957
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