间质干细胞（ MSCS ）是一类具有多向分化潜能的细胞类型,越来越多地报告显示该细胞有利于的器官损伤模式的修复.然而,间充质干细胞和宿主细胞分子之间的相互作用机制仍不清楚,特别是血管内皮细胞（ECs）.我们发现在基底膜血管生成法中间充质干细胞能抑制毛细血管的增长.在基底膜中EC衍生的毛细血管中加入MSCS,ES:MSCS 比率1：1.MSCS 移行向毛细管间生在连接蛋白43,与ECs在细胞间隙结合,增加生产ROS,这导致细胞凋亡和EC衍生的毛细血管变性.在活体肿瘤模型中,直接接种MSC到皮肤黑色素瘤中诱导细胞凋亡和抑制肿瘤的生长.因此,我们的研究结果首次表明,MSCS具有潜在细胞毒性,在肿瘤组织中局部注射时,能有效的抑制血管生成而适用于癌症的治疗.

  Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells
  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.

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