Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells
Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells
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DOI：
10.1182/blood-2008-09-176198
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发表时间：
2009-04-30
期刊：
影响因子：
20.3
通讯作者：
Bhattacharya, Jahar
中科院分区：
文献类型：
--
作者：
Otsu, Keishi;Das, Shonit;Bhattacharya, Jahar
间充质干细胞（MSC），有可能转分化成多种细胞类型，越来越多的报道是有益的器官系统损伤模型。然而，MSC和宿主细胞，特别是内皮细胞（EC）之间相互作用的分子机制仍不清楚。我们在基质胶血管生成试验中显示，MSC能够抑制毛细血管生长。以EC：MSC = 1：1的比例将MSC加入基质胶中的EC衍生毛细血管后，MSC向毛细血管迁移，插入EC之间，与EC建立基于Cx43的细胞间间隙连接通讯（GJC），并增加活性氧（ROS）的产生。这些事件导致EC凋亡和毛细血管变性。在体内肿瘤模型中，将MSC直接接种到皮下黑色素瘤中诱导细胞凋亡并消除肿瘤生长。因此，我们的研究结果首次表明，在高数量下，MSC具有潜在的细胞毒性，并且当局部注射到肿瘤组织中时，它们可能是适用于癌症治疗的有效抗血管生成剂。（血。2009; 113：4197-4205）
Mesenchymal stem cells (MSCs), which potentially transdifferentiate into multiple cell types, are increasingly reported to be beneficial in models of organ system injury. However, the molecular mechanisms underlying interactions between MSCs and host cells, in particular endothelial cells (ECs), remain unclear. We show here in a matrigel angiogenesis assay that MSCs are capable of inhibiting capillary growth. After addition of MSCs to EC-derived capillaries in matrigel at EC: MSC ratio of 1: 1, MSCs migrated toward the capillaries, intercalated between ECs, established Cx43-based intercellular gap junctional communication (GJC) with ECs, and increased production of reactive oxygen species (ROS). These events led to EC apoptosis and capillary degeneration. In an in vivo tumor model, direct MSC inoculation into subcutaneous melanomas induced apoptosis and abrogated tumor growth. Thus, our findings show for the first time that at high numbers, MSCs are potentially cytotoxic and that when injected locally in tumor tissue they might be effective antiangiogenesis agents suitable for cancer therapy. (Blood. 2009; 113: 4197-4205)