Early lymph vessel development from embryonic stem cells
Early lymph vessel development from embryonic stem cells
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DOI：
10.1161/01.atv.0000217610.58032.b7
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发表时间：
2006-05-01
影响因子：
8.7
通讯作者：
Claesson-Welsh, L
中科院分区：
文献类型：
--
作者：
Kreuger, J;Nilsson, I;Claesson-Welsh, L
目的 - 本研究的目的是建立基于小鼠胚胎干细胞定向分化的淋巴管发育模型系统。方法和结果 - 干细胞聚集形成胚状体，随后在 3 维胶原蛋白基质中培养长达 18 天。血管内皮生长因子 (VEGF)-C 和 VEGF-A 的治疗分别增强了淋巴管结构的形成，尽管 VEGF-C 和 VEGF-A 的联合治疗最有效，并且产生了 LYVE-1、podoplanin、Prox1 和 VEGF 受体 3 阳性淋巴管结构的网络，该网络平行于毛细血管运行并明显源自毛细血管。相反，成纤维细胞生长因子-2、肝细胞生长因子或缺氧对早期淋巴管的发育影响很小或没有影响。此外，造血来源的细胞显示出表达淋巴标记物。总之，根据几种淋巴管和血管标记物的差异表达，鉴定了不同的淋巴管内皮细胞亚群，表明血管异质性。结论 - 我们得出的结论是，本模型密切模仿小鼠胚胎中淋巴管发育的早期步骤。
Objective - The purpose of this study was to establish a model system for lymph vessel development based on directed differentiation of murine embryonic stem cells.Methods and Results - Stem cells were aggregated to form embryoid bodies, and subsequently cultured in 3-dimensional collagen matrix for up to 18 days. Treatment with vascular endothelial growth factor ( VEGF)- C and VEGF-A individually enhanced formation of lymphatic vessel structures, although combined treatment with VEGF-C and VEGF-A was most potent and gave rise to a network of LYVE-1, podoplanin, Prox1, and VEGF receptor-3 positive lymphatic vessel structures running parallel to and apparently emanating from, capillaries. In contrast, fibroblast growth factor-2, hepatocyte growth factor, or hypoxia had little or no effect on the development of the early lymphatics. Further, cells of hematopoietic origin were shown to express lymphatic markers. In summary, different subpopulations of lymphatic endothelial cells were identified on the basis of differential expression of several lymphatic and blood vessel markers, indicating vascular heterogeneity.Conclusions - We conclude that the present model closely mimics the early steps of lymph vessel development in mouse embryos.