Differentiation of Multipotent Adult Germline Stem Cells Derived from Mouse Testis into Functional Endothelial Cells
Differentiation of Multipotent Adult Germline Stem Cells Derived from Mouse Testis into Functional Endothelial Cells
复制标题
小鼠睾丸来源的多能成体生殖干细胞分化为功能性内皮细胞
DOI：
10.1159/000332910
复制
发表时间：
2012
影响因子：
1.7
通讯作者：
Schaefer K
中科院分区：
文献类型：
--
作者：
Cheng I-F;Kaiser D;Hübscher D;Hasenfuss G;Guan K;Schaefer K
多能干细胞在心血管疾病的治疗方面大有可为。我们先前描述了来自小鼠睾丸的多潜能成体生殖系干细胞(MaGSCs)具有类似于胚胎干细胞的分化潜能。本研究的目的是将大鼠骨髓间充质干细胞分化为具有功能的内皮细胞，并研究其血管生成的潜力。MaGSCs与OP9基质细胞共培养，诱导分化为心血管前体细胞，即胎肝激酶1阳性(Flk-1+)细胞。5天后，用荧光激活细胞分选法分离Flk-1+细胞，然后在内皮分化条件下培养IV型胶原。在不同时间点，采用RT-PCR、流式细胞仪、免疫荧光和功能分析等方法对MAGSC来源的内皮样细胞进行鉴定。培养Flk-1+细胞后，VE-钙粘蛋白、von Willebrand因子和内皮型一氧化氮合酶等内皮细胞标志物表达逐渐上调。此外，Flk-1+maGSC来源的内皮样细胞在体外能够分支并形成网络，并在体内促进功能性血管的形成。重要的是，Flk-1+细胞在保持接触抑制能力的同时，保留了其增殖和持续扩增的能力。因此，MAGSC可能为研究血管生成或内皮细胞分化的基本机制提供有用的内皮样细胞来源。
Pluripotent stem cells hold great promise for the treatment of cardiovascular disease. We previously described multipotent adult germline stem cells (maGSCs) from mouse testis with differentiation potential similar to embryonic stem cells. The aim of this work was to differentiate maGSCs into functional endothelial cells and to study their potential for vasculogenesis. MaGSCs were cocultivated with OP9 stromal cells to induce differentiation into cardiovascular progenitors, ie fetal liver kinase 1-positive (Flk-1+) cells. Five days later, Flk-1+ cells were separated using fluorescence-activated cell sorting, followed by cultivation on collagen type IV under endothelial differentiation conditions. At different time points, maGSC-derived endothelial-like cells were characterized using RT-PCR, flow cytometry, immunofluorescence and functional assays. Cultivation of Flk-1+ cells resulted in the progressive upregulation of endothelial cell markers, including VE-cadherin, von Willebrand factor and endothelial nitric oxide synthase. Moreover, Flk-1+ maGSC-derived endothelial-like cells were able to branch and form networks in vitro and promoted functional blood vessel formation in vivo. Importantly, Flk-1+ cells retained their potential to proliferate and could be continuously expanded, while the ability of contact inhibition was preserved. Thus, maGSCs may provide a useful source of endothelial-like cells to study the basic mechanisms of vasculogenesis or endothelial differentiation.
登录
查看更多内容
影响因子：
2.9
作者：
Nolte, Jessica;Michelmann, Hans W.;Engel, Wolfgang
通讯作者：
Engel, Wolfgang
影响因子：
20.3
作者：
Vodyanik, MA;Bork, JA;Slukvin, II
通讯作者：
Slukvin, II
DOI：
10.1073/pnas.97.7.3422
发表时间：
2000-03
影响因子：
11.1
作者：
C. Kalka;H. Masuda;Tomono Takahashi;W. Kalka-Moll;Marcy Silver;M. Kearney;Tong Li;J. Isner
通讯作者：
C. Kalka;H. Masuda;Tomono Takahashi;W. Kalka-Moll;Marcy Silver;M. Kearney;Tong Li;J. Isner
影响因子：
64.8
作者：
Yang, Lei;Soonpaa, Mark H.;Keller, Gordon M.
通讯作者：
Keller, Gordon M.
影响因子：
20.3
作者：
W. Zhang;Changwon Park;Elizabeth Arentson;Kyunghee Choi
通讯作者：
W. Zhang;Changwon Park;Elizabeth Arentson;Kyunghee Choi