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CC BY 4.0 · J Reconstr Microsurg
DOI: 10.1055/a-2687-0506
Original Article

A Novel Lymphosome-Based Long-Lasting Rat Tail Model of Lymphedema

Junzhe Chen
1   Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
,
Yun Wang
1   Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
,
Shilin Tu
1   Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
,
Yan Zhou
1   Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
,
Haokun Qin
1   Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
,
Zeyao Tang
1   Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
,
Yuezhong Chen
1   Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
,
Shune Xiao   ‡
1   Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
2   The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou, China
,
Chengliang Deng   ‡
1   Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
2   The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou, China
› Institutsangaben
Funding Ministry of Science and Technology of the People's Republic of China. National Natural Science Foundation of China. 82260391. 82372541. Talent Team Construction Project for Basic and Clinical Research on Lymphedema of Guizhou Province x. Qiankehe Talent CXTD [2025] 051.
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Abstract

Background

Secondary extremity lymphedema is a chronic and progressive condition caused by obstructed lymphatic drainage, commonly following lymphadenectomy, infection, or trauma. Rodent models are preferred for experimental lymphedema research due to cost-effectiveness and reproducibility. Currently, rat tail models encounter limitations due to transient swelling and their inability to fully replicate the comprehensive pathophysiology of lymphedema, particularly concerning the effects of lymph node removal.

Methods

We developed a series of rat tail lymphedema models incorporating skin resection, deep lymphatic vessel disruption, and gluteal lymph node (GLN) excision to assess effects on lymphatic architecture, inflammation, and fibrosis. Indocyanine green (ICG) lymphography was used to visualize lymphatic function. Tail volume and circumference were measured weekly, and histological assessments quantified fibrosis and fibroadipose thickening. Bulk RNA sequencing was performed to characterize the inflammatory processes triggered by GLN removal.

Results

The combined model (skin removal, deep lymphatic disruption, and GLN excision) resulted in severe and persistent lymphedema marked by progressive swelling and pronounced fibrosis. ICG lymphography confirmed disruption of superficial lymphatic flow with partial recanalization of deep channels. Notably, lymphangiogenesis was observed at the GLN excision site, forming compensatory pathways connecting the tail to the popliteal lymph nodes. Histology revealed extensive collagen deposition and fibroadipose thickening in groups with lymph node removal, with the combined model showing the most pronounced changes. Bulk RNA-sequencing confirmed the removal of GLN involving the inflammatory and fibrosis process in the tail model.

Conclusion

This lymphosome-based rat tail model successfully replicates key features of lymphedema, including sustained swelling, lymphatic disruption, inflammation, and fibrosis.

Keywords

lymphedema - animal model - tail

‡ These authors contributed equally to this article.


Supplementary Material



Publikationsverlauf

Eingereicht: 01. Mai 2025

Angenommen: 17. August 2025

Accepted Manuscript online:
21. August 2025

Artikel online veröffentlicht:
03. September 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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