Cardiovascular Research Center, The Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Thromb Haemost. 2010 Jan;103(1):188-97. doi: 10.1160/TH09-07-0433. Epub 2009 Oct 26.
The LIM-homeobox transcription factor islet-1 (Isl1) marks a cell population which gives rise to myocardial, pacemaker, endothelial and smooth muscle cells, which are derived from the secondary heart field during heart embryogenesis. Isl1+ precursors have the potential of self-renewal and differentiation into endothelial, cardiomyocyte and smooth muscle lineages. The primary objective of this study was to determine whether retroviral gene delivery of Isl1 to endothelial cells and mesenchymal stem cells (MSCs) could promote angiogenic and vasculogenic properties. To this end, endothelial cells and rat MSCs were retrovirally transduced to express Isl1. Isl1 expression in endothelial cells resulted in enhanced proliferation and adhesion to fibronectin. In addition, increased IL-1b and VEGF secretion was evident in Isl1 transduced endothelial cells, concomitant with increased migratory and tube formation properties of the endothelial cells. Isl1 expression in MSCs promoted their vasculogenic properties and resulted in enhanced in vitro tube formation. Finally, Isl1 expressing endothelial cells induced enhanced in vivo vascularisation in C57BL/6J mice. These data suggest, for the first time, that Isl1 promotes postnatal angiogenesis and vasculogenesis by improving the angiogenic properties of endothelial cells and MSCs.
LIM 同源盒转录因子胰岛 1（Isl1）标记了一个细胞群体，该群体产生心肌细胞、起搏细胞、内皮细胞和平滑肌细胞，这些细胞是心脏胚胎发生过程中从次级心脏场衍生而来的。Isl1+前体细胞具有自我更新和分化为内皮细胞、心肌细胞和平滑肌谱系的潜力。本研究的主要目的是确定是否可以通过逆转录病毒基因传递将 Isl1 传递到内皮细胞和间充质干细胞（MSCs）中，以促进血管生成和血管生成特性。为此，将内皮细胞和大鼠 MSCs 逆转录病毒转导以表达 Isl1。内皮细胞中 Isl1 的表达导致增殖和对纤维连接蛋白的粘附增强。此外，Isl1 转导的内皮细胞中明显增加了白细胞介素 1b 和 VEGF 的分泌，同时内皮细胞的迁移和管状形成特性也增加。MSCs 中 Isl1 的表达促进了它们的血管生成特性，并导致体外管状形成增强。最后，表达 Isl1 的内皮细胞诱导 C57BL/6J 小鼠体内血管生成增强。这些数据首次表明，Isl1 通过改善内皮细胞和 MSCs 的血管生成特性来促进成年后的血管生成和血管生成。
