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通过工程化外泌体递送血管内皮生长因子（VEGFC）可改善淋巴水肿。

Delivery of vascular endothelial growth factor (VEGFC) via engineered exosomes improves lymphedema.

作者信息

Li Bohan, Yang Jiantao, Wang Raoping, Li Jia, Li Xubo, Zhou Xiang, Qiu Shuai, Weng Ricong, Wu Zichao, Tang Chunyuan, Li Ping

机构信息

Department of Microsurgery & Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

出版信息

Ann Transl Med. 2020 Nov;8(22):1498. doi: 10.21037/atm-20-6605.

DOI:10.21037/atm-20-6605
PMID:33313243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7729376/
Abstract

BACKGROUND

Lymphedema is a chronic disease results from impaired flow of the lymphatic system. Therefore, reconstruction of lymphatic system is crucial to treat limb lymphedema. Vascular endothelial growth factor (VEGFC) has been reported to be an important regulator involved in the growth and differentiation of lymphatic endothelial cells; however; the application of exosomes with VEGFC in the treatment of lymphedema has been rarely reported.

METHODS

From the membrane-based fusion technology, we constructed engineered exosomes that overexpress CD63-VEGFC fusion protein (CD63-VEGFC/exos). We examined the effects of CD63-VEGFC/exos on the proliferation, migration, and tube formation of human dermal lymphatic endothelial cells (HDLECs) by MTT assay, migration assay, and tube formation assay, respectively. CD63-VEGFC/exos were embedded in sodium alginate hydrogel and their effect on lymphedema was evaluated by a mouse model.

RESULTS

VEGFC could be successfully delivered to lymphatic endothelial cells via engineered CD63-VEGFC/exos. Treatment with CD63-VEGFC/exos resulted in a significant increase in the proliferation, migration, and tube formation of lymphatic endothelial cells. Using CD63-VEGFC/egos in sodium alginate hydrogel enabled a sequenced release of exosomes and markedly improved lymphedema in a mouse model.

CONCLUSIONS

Our findings supply a novel adipose tissue-derived stem cell (ADSC)-exo-based strategy that delivers target proteins to lymphatic endothelial cells and thus enhances the treatment of lymphedema.

摘要

背景

淋巴水肿是一种因淋巴系统流动受损导致的慢性疾病。因此，淋巴系统重建对于治疗肢体淋巴水肿至关重要。据报道，血管内皮生长因子（VEGFC）是参与淋巴管内皮细胞生长和分化的重要调节因子；然而，载有VEGFC的外泌体在淋巴水肿治疗中的应用鲜有报道。

方法

利用基于膜的融合技术，我们构建了过表达CD63-VEGFC融合蛋白的工程外泌体（CD63-VEGFC/exos）。我们分别通过MTT法、迁移试验和管腔形成试验检测了CD63-VEGFC/exos对人真皮淋巴管内皮细胞（HDLECs）增殖、迁移和管腔形成的影响。将CD63-VEGFC/exos包埋于海藻酸钠水凝胶中，并通过小鼠模型评估其对淋巴水肿的作用。

结果

VEGFC可通过工程化的CD63-VEGFC/exos成功递送至淋巴管内皮细胞。用CD63-VEGFC/exos处理导致淋巴管内皮细胞的增殖、迁移和管腔形成显著增加。在海藻酸钠水凝胶中使用CD63-VEGFC/外泌体能够实现外泌体的顺序释放，并显著改善小鼠模型中的淋巴水肿。

结论

我们的研究结果提供了一种基于新型脂肪组织来源干细胞（ADSC）外泌体的策略，该策略可将靶蛋白递送至淋巴管内皮细胞，从而增强对淋巴水肿的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/cb474044a02d/atm-08-22-1498-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/4c9134c3b02e/atm-08-22-1498-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/6930ac94fad4/atm-08-22-1498-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/5e87f6748ea8/atm-08-22-1498-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/15076d6e2563/atm-08-22-1498-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/cb474044a02d/atm-08-22-1498-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/4c9134c3b02e/atm-08-22-1498-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/6930ac94fad4/atm-08-22-1498-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/5e87f6748ea8/atm-08-22-1498-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/15076d6e2563/atm-08-22-1498-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7729376/cb474044a02d/atm-08-22-1498-f5.jpg

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