Adipose-Derived Stem Cells Promote Intussusceptive Lymphangiogenesis by Restricting Dermal Fibrosis in Irradiated Tissue of Mice
Adipose-Derived Stem Cells Promote Intussusceptive Lymphangiogenesis by Restricting Dermal Fibrosis in Irradiated Tissue of Mice
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DOI：
10.3390/ijms21113885
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发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Morita, Eishin
中科院分区：
文献类型：
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作者：
Ogino, Ryohei;Hayashida, Kenji;Morita, Eishin
目前，淋巴系统疾病还没有明确的治疗方法。脂肪源性干细胞（ADSCs）已被报道可促进水肿模型的淋巴再生，但其治疗作用的机制尚不清楚。在这里，我们使用继发性水肿小鼠模型测试ADSC移植对水肿的治疗效果。通过X射线照射和原位手术切除淋巴系统在C57 BL/6 J小鼠中建立模型。在接受7.5 × 10（5）ADSC移植的小鼠中，具有抗淋巴管内皮透明质酸受体1（LYVE-1）免疫反应性的淋巴管数量显著增加。X射线照射抑制淋巴管扩张，ADSC移植可以减轻。淋巴细胞核抗原染色显示淋巴管内皮细胞（LEC）和细胞外基质增殖增加。天狼星红染色显示ADSC移植后真皮组织中胶原纤维的方向正常。这些治疗效果与血管内皮生长因子（VEGF）-C表达无关。扫描电子显微镜显示结构相似的管腔内柱在血管生成过程中的扩张的淋巴管的内部。我们预测在水肿中会发生内陷性淋巴管生成。我们的研究结果表明，ADSC移植有助于减轻水肿，通过促进LEC增殖，改善纤维化和淋巴管的扩张能力，并增加淋巴管的数量，通过intulluctively淋巴管生成。
Currently, there is no definitive treatment for lymphatic disorders. Adipose-derived stem cells (ADSCs) have been reported to promote lymphatic regeneration in lymphedema models, but the mechanisms underlying the therapeutic effects remain unclear. Here, we tested the therapeutic effects of ADSC transplantation on lymphedema using a secondary lymphedema mouse model. The model was established in C57BL/6J mice by x-irradiation and surgical removal of the lymphatic system in situ. The number of lymphatic vessels with anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunoreactivity increased significantly in mice subjected to transplantation of 7.5 x 10(5) ADSCs. X-irradiation suppressed lymphatic vessel dilation, which ADSC transplantation could mitigate. Proliferative cell nuclear antigen staining showed increased lymphatic endothelial cell (LEC) and extracellular matrix proliferation. Picrosirius red staining revealed normal collagen fiber orientation in the dermal tissue after ADSC transplantation. These therapeutic effects were not related to vascular endothelial growth factor (VEGF)-C expression. Scanning electron microscopy revealed structures similar to the intraluminal pillar during intussusceptive angiogenesis on the inside of dilated lymphatic vessels. We predicted that intussusceptive lymphangiogenesis occurred in lymphedema. Our findings indicate that ADSC transplantation contributes to lymphedema reduction by promoting LEC proliferation, improving fibrosis and dilation capacity of lymphatic vessels, and increasing the number of lymphatic vessels via intussusceptive lymphangiogenesis.