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小型猪模型中无血管淋巴结碎片移植技术的比较以优化淋巴管生成

Comparison of avascular lymph node fragment transplantation techniques to optimize lymphangiogenesis in the minipig model.

作者信息

Hadamitzky Catarina, Bruns Frank, Gratz Klaus-Friedrich, Schindewolffs Lia, Roth Katrin S, Werner Martin, Gordon Kristiana, Vogt Peter M, Pabst Reinhard

机构信息

Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover, Germany.

Hannover, Germany.

出版信息

Eur J Plast Surg. 2022;45(1):55-64. doi: 10.1007/s00238-021-01869-3. Epub 2021 Oct 12.

DOI:10.1007/s00238-021-01869-3
PMID:35210698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8818007/
Abstract

BACKGROUND

Secondary lymphoedema is a challenging pandemic. This condition may arise after oncologic resection of tumor-draining lymph nodes and/or radiation. Plastic-surgical procedures for lymphoedema comprise transplantation of vascularized lymph node flaps, which are, however, technically challenging and difficult to implement on a global level due to the scarcity of microsurgery facilities in some countries. To improve this situation, comparative research in valid animal models is needed.

METHODS

A total of 33 minipigs were subjected to lymphatic resection in the hind limbs. This large animal model was used in a first phase to compare different lymph node fragmentation methods and assess lymphatic regeneration after avascular transplantation. In a second phase, several stimulants were tested for their effect on lymphatic regeneration after fragment transplantation. In a third phase, animals additionally received irradiation of the groin. In this novel animal model, autologous avascular lymph node fragment transplantation was complemented by peripheral injections of vascular endothelial growth factor-C (VEGF-C). Finally, regeneration rates were quantified in relative numbers (percentage) in the irradiated tissue.

RESULTS

In the first phase, transversal lymph node fragmentation under preservation of the nodal capsule showed the best percentage of regeneration (62.5%). Peripheral intradermal administration of VEGF-C enhanced lymph node fragment regeneration (70.8%) better than injections of tetanus toxoid (41.6%) or (62.5%). Lymph node fragment regeneration also occurred in an irradiated porcine model of lymphadenectomy under VEGF-C administration (66.6%).

CONCLUSIONS

The present findings provide a pre-clinical proof-of-concept for a possible simplification strategy for current operative procedures of autologous lymph node transplantation.Level of evidence : Not gradable.

摘要

背景

继发性淋巴水肿是一个具有挑战性的全球性问题。这种情况可能在肿瘤引流淋巴结的肿瘤切除和/或放疗后出现。淋巴水肿的整形手术包括带血管蒂淋巴结瓣移植,然而,由于一些国家显微外科设施的稀缺,该技术具有挑战性且难以在全球范围内实施。为改善这种情况,需要在有效的动物模型中进行比较研究。

方法

总共33只小型猪接受后肢淋巴管切除术。在第一阶段使用这个大型动物模型来比较不同的淋巴结破碎方法,并评估无血管移植后的淋巴再生情况。在第二阶段,测试了几种刺激物对碎片移植后淋巴再生的影响。在第三阶段,动物还接受腹股沟照射。在这个新的动物模型中,自体无血管淋巴结碎片移植辅以血管内皮生长因子-C(VEGF-C)的外周注射。最后,在照射组织中以相对数量(百分比)对再生率进行量化。

结果

在第一阶段,保留淋巴结包膜的横向淋巴结破碎显示出最佳的再生百分比(62.5%)。外周皮内注射VEGF-C比注射破伤风类毒素(41.6%)或[此处原文缺失内容](62.5%)能更好地促进淋巴结碎片再生(70.8%)。在VEGF-C给药的照射猪淋巴结切除模型中也发生了淋巴结碎片再生(66.6%)。

结论

本研究结果为当前自体淋巴结移植手术程序可能的简化策略提供了临床前概念验证。证据水平:不可分级。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dec5/8818007/6b32ce78e4b8/238_2021_1869_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dec5/8818007/a067c77a03f9/238_2021_1869_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dec5/8818007/5cb129be5825/238_2021_1869_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dec5/8818007/6b32ce78e4b8/238_2021_1869_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dec5/8818007/a067c77a03f9/238_2021_1869_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dec5/8818007/5cb129be5825/238_2021_1869_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dec5/8818007/6b32ce78e4b8/238_2021_1869_Fig3_HTML.jpg

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