Mesenchymal stem cells promote lymphangiogenic properties of lymphatic endothelial cells.
Mesenchymal stem cells promote lymphangiogenic properties of lymphatic endothelial cells.
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DOI：
10.1111/jcmm.13590
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发表时间：
2018-08
影响因子：
5.3
通讯作者：
Boos AM
中科院分区：
文献类型：
--
作者：
Robering JW;Weigand A;Pfuhlmann R;Horch RE;Beier JP;Boos AM
淋巴结转移是影响癌症患者长期生存的主要预后因素之一。在这方面，淋巴管生成的分子机制仍然很少探索。此外，人类干细胞和淋巴管内皮细胞（LEC）之间的相互作用尚未得到很好的研究。因此，本研究的主要目的是评估间充质干细胞（MSC）和LEC之间的相互作用，使用体外血管生成试验。用VEGF-C、bFGF、MSC条件培养基（MSC-CM）或通过与MSC共培养来刺激幼年LEC。采用MTT法检测LEC增殖情况。用伤口愈合测定和迁移测定确定细胞的迁移。为了测量淋巴芽的形成，将LEC球状体包埋在胶原蛋白或纤维蛋白凝胶中。LEC形成毛细血管样结构的能力通过Matrigel®上的管形成测定来评估。MSC-CM及与MSC共培养均能显著促进LEC的增殖、迁移和管腔形成。在增殖和迁移测定中，与生长因子VEGF-C和bFGF刺激相比，用MSC-CM刺激的效果更强。VEGF-C、bFGF和MSC-CM刺激发芽。通过这项研究，我们证明了MSC分泌蛋白组对LEC增殖、迁移和管形成的有效刺激作用。这表明MSC在病理和生理过程中的淋巴管生成中起重要作用。
Lymphatic metastasis is one of the main prognostic factors concerning long‐term survival of cancer patients. In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not been well examined. Therefore, the main objective of this study was to assess the interactions between mesenchymal stem cells (MSC) and LEC using in vitro angiogenesis assays. Juvenile LEC were stimulated with VEGF‐C, bFGF, MSC‐conditioned medium (MSC‐CM) or by co‐culture with MSC. LEC proliferation was assessed using a MTT assay. Migration of the cells was determined with a wound healing assay and a transmigration assay. To measure the formation of lymphatic sprouts, LEC spheroids were embedded in collagen or fibrin gels. The LEC's capacity to form capillary‐like structures was assessed by a tube formation assay on Matrigel®. The proliferation, migration and tube formation of LEC could be significantly enhanced by MSC‐CM and by co‐culture with MSC. The effect of stimulation with MSC‐CM was stronger compared to stimulation with the growth factors VEGF‐C and bFGF in proliferation and transmigration assays. Sprouting was stimulated by VEGF‐C, bFGF and by MSC‐CM. With this study, we demonstrate the potent stimulating effect of the MSC secretome on proliferation, migration and tube formation of LEC. This indicates an important role of MSC in lymphangiogenesis in pathological as well as physiological processes.
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影响因子：
5.3
作者：
Horch RE;Beier JP;Kneser U;Arkudas A
通讯作者：
Arkudas A
影响因子：
20.3
作者：
Bignon, Marine;Pichol-Thievend, Cathy;Germain, Stephane
通讯作者：
Germain, Stephane
DOI：
10.1073/pnas.0900244106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Coffelt, Seth B.;Marini, Frank C.;Scandurro, Aline B.
通讯作者：
Scandurro, Aline B.
影响因子：
9.8
作者：
Dietrich, Franziska;Lelkes, Peter I.
通讯作者：
Lelkes, Peter I.
DOI：
10.1152/ajpheart.01071.2003
发表时间：
2004-12-01
影响因子：
4.8
作者：
Nagaya, N;Fujii, T;Kitamura, S
通讯作者：
Kitamura, S