Department of Biomedical Laboratory Science, Honam University, Gwangju, 62399, Republic of Korea.
Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Republic of Korea.
Sci Rep. 2023 Apr 3;13(1):5397. doi: 10.1038/s41598-023-32473-z.
To overcome the limitations of lymphedema treatment, human adipose-derived stem cells (hADSCs) were injected into decellularized lymph nodes to produce a recellularized lymph node-scaffold, and the effect of lymphangiogenesis was investigated in lymphedema animal models. Axillary lymph nodes were harvested from Sprague Dawley rats (7 weeks old, 220-250 g) for decellularization. The decellularized lymph nodes were performed and PKH26-labeled hADSCs (1 × 10/50 µL) were injected in the decellularized lymph node-scaffolds. Forty rats were equally divided into four groups: lymphedema as control group, hADSC group, decellularized lymph node-scaffold group, and recellularized lymph node-scaffold group. The lymphedema model was made by removing inguinal lymph nodes, and hADSCs or scaffolds were transplanted. Histopathological assessments were performed by hematoxylin and eosin and Masson's trichrome staining. Lymphangiogenesis was evaluated by Immunofluorescence staining and western blot. Decellularized lymph nodes showed virtually complete absence of cellular material and maintenance of lymph node architecture. The hADSCs were significantly observed in recellularized lymph node-scaffolds group. The recellularized lymph node-scaffold group was histologically similar to normal lymph nodes. The vascular endothelial growth factor A and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) in immunofluorescence staining were highly expressed in recellularized lymph node-scaffolds group. Also, the expression of LYVE-1 protein significantly increased in recellularized lymph node-scaffold group compared with others. Recellularized lymph node -scaffold had a much better therapeutic effect than stem cells or decellularized lymph node-scaffold alone, and induced stable lymphangiogenesis.
为了克服淋巴水肿治疗的局限性，将人脂肪来源干细胞（hADSCs）注入去细胞化的淋巴结中以产生再细胞化的淋巴结支架，并在淋巴水肿动物模型中研究了淋巴管生成的效果。从 Sprague Dawley 大鼠（7 周龄，220-250g）中收获腋窝淋巴结进行去细胞化。进行去细胞化的淋巴结，并将 PKH26 标记的 hADSCs（1×10/50µL）注入去细胞化的淋巴结支架中。将 40 只大鼠等分为四组：淋巴水肿为对照组、hADSC 组、去细胞化淋巴结支架组和再细胞化淋巴结支架组。通过去除腹股沟淋巴结来建立淋巴水肿模型，并移植 hADSCs 或支架。通过苏木精和伊红及 Masson 三色染色进行组织病理学评估。通过免疫荧光染色和 Western blot 评估淋巴管生成。去细胞化的淋巴结几乎完全没有细胞物质且保持淋巴结结构。在再细胞化的淋巴结支架组中明显观察到 hADSCs。再细胞化的淋巴结支架组在组织学上类似于正常淋巴结。在免疫荧光染色中，血管内皮生长因子 A 和淋巴管内皮透明质酸受体 1（LYVE-1）高度表达。此外，与其他组相比，再细胞化的淋巴结支架组中 LYVE-1 蛋白的表达显著增加。与单独的干细胞或去细胞化的淋巴结支架相比，再细胞化的淋巴结支架具有更好的治疗效果，并诱导稳定的淋巴管生成。
