Paracrine factors released by GATA-4 overexpressed mesenchymal stem cells increase angiogenesis and cell survival
Paracrine factors released by GATA-4 overexpressed mesenchymal stem cells increase angiogenesis and cell survival
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DOI：
10.1152/ajpheart.00557.2010
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发表时间：
2010-12-01
影响因子：
4.8
通讯作者：
Xu, Meifeng
中科院分区：
文献类型：
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作者：
Li, Hongxia;Zuo, Shi;Xu, Meifeng
李华，左S，何Z，杨Y，Pasha Z，王Y，徐M.由加塔-4过表达的间充质干细胞释放的旁分泌因子增加血管生成和细胞存活。美国生理学杂志心脏循环生理学299：H1772-H1781，2010年。首次发表于2010年9月24日; doi：10.1152/ajpheart.00557.2010.-移植的间充质干细胞（MSC）释放有助于心脏修复和血管再生的可溶性因子。我们假设加塔-4的过表达增强了MSC分泌组，从而增加了细胞存活率并促进了梗死后心脏血管生成。使用鼠干细胞病毒逆转录病毒表达系统，用加塔-4（MSC加塔-4）转导从雄性大鼠骨髓收获的MSC;对照细胞为未转导的（MSCbas）或用空载体转导的（MSCbas）。免疫荧光、实时荧光定量PCR和Western blotting检测结果显示，与对照细胞相比，MSC加塔-4细胞中加塔-4的表达量更高。MSCGATA-4中血管生成因子的表达增加，MSC对缺氧的抵抗力增强。与用MSCGATA-4条件培养基处理的人脐静脉内皮细胞（HUVEC）相比，用MSCGATA-4条件培养基处理的HUVEC表现出毛细血管样结构的形成增加，并促进迁移。将MSCGATA-4注射到通过结扎冠状动脉左前降支建立的Sprague-Dawley大鼠急性心肌梗死模型的梗死周围区域。MSCGATA-4的存活率（通过Sry表达确定）在移植后4天增加。经超声心动图评估，MSCGATA-4处理的动物显示心脏功能显著改善。此外，荧光微球和组织学研究显示，MSC GATA-4治疗的动物血流量和血管密度增加，梗死面积缩小。我们的结论是，加塔-4在MSC中的过表达增加了缺血心肌中MSC的存活率和血管生成潜力，因此可能代表了一种新的和有效的治疗梗死后重构的方法。
Li H, Zuo S, He Z, Yang Y, Pasha Z, Wang Y, Xu M. Paracrine factors released by GATA-4 overexpressed mesenchymal stem cells increase angiogenesis and cell survival. Am J Physiol Heart Circ Physiol 299: H1772-H1781, 2010. First published September 24, 2010; doi:10.1152/ajpheart.00557.2010.-Transplanted mesenchymal stem cells (MSC) release soluble factors that contribute to cardiac repair and vascular regeneration. We hypothesized that overexpression of GATA-4 enhances the MSC secretome, thereby increasing cell survival and promoting postinfarction cardiac angiogenesis. MSCs harvested from male rat bone marrow were transduced with GATA-4 (MSCGATA-4) using the murine stem cell virus retroviral expression system; control cells were either nontransduced (MSCbas) or transduced with empty vector (MSCNull). Compared with these control cells, MSCGATA-4 were shown by immunofluorescence, real-time PCR, and Western blotting to have higher expression of GATA-4. An increased expression of angiogenic factors in MSCGATA-4 and higher MSC resistance against hypoxia were observed. Human umbilical vein endothelial cells (HUVEC) treated with MSCGATA-4 conditioned medium exhibited increased formation of capillary-like structures and promoted migration, compared with HUVECs treated with MSCNull conditioned medium. MSCGATA-4 were injected into the peri-infarct region in an acute myocardial infarction model in Sprague-Dawley rats developed by ligation of the left anterior descending coronary artery. Survival of MSCGATA-4, determined by Sry expression, was increased at 4 days postengraftment. MSCGATA-4-treated animals showed significantly improved cardiac function as assessed by echocardiography. Furthermore, fluorescent microsphere and histological studies revealed increased blood flow and blood vessel density and reduced infarction size in MSCGATA-4-treated animals. We conclude that GATA-4 overexpression in MSCs increased both MSC survival and angiogenic potential in ischemic myocardium and may therefore represent a novel and efficient therapeutic approach for postinfarct remodeling.