Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac 15-21, 08028 Barcelona, Spain.
Biochem Biophys Res Commun. 2010 Sep 17;400(2):284-91. doi: 10.1016/j.bbrc.2010.08.073. Epub 2010 Aug 21.
Tissue engineering aims to regenerate tissues and organs by using cell and biomaterial-based approaches. One of the current challenges in the field is to promote proper vascularization in the implant to prevent cell death and promote host integration. Bone marrow endothelial progenitor cells (BM-EPCs) and mesenchymal stem cells (MSCs) are bone marrow resident stem cells widely employed for proangiogenic applications. In vivo, they are likely to interact frequently both in the bone marrow and at sites of injury. In this study, the physical and biochemical interactions between BM-EPCs and MSCs in an in vitro co-culture system were investigated to further clarify their roles in vascularization. BM-EPC/MSC co-cultures established close cell-cell contacts soon after seeding and self-assembled to form elongated structures at 3days. Besides direct contact, cells also exhibited vesicle transport phenomena. When co-cultured in Matrigel, tube formation was greatly enhanced even in serum-starved, growth factor free medium. Both MSCs and BM-EPCs contributed to these tubes. However, cell proliferation was greatly reduced in co-culture and morphological differences were observed. Gene expression and cluster analysis for wide panel of angiogenesis-related transcripts demonstrated up-regulation of angiogenic markers but down-regulation of many other cytokines. These data suggest that cross-talk occurs in between BM-EPCs and MSCs through paracrine and direct cell contact mechanisms leading to modulation of the angiogenic response.
组织工程旨在通过细胞和基于生物材料的方法来再生组织和器官。该领域目前面临的挑战之一是在植入物中促进适当的血管生成，以防止细胞死亡和促进宿主整合。骨髓内皮祖细胞（BM-EPC）和间充质干细胞（MSC）是广泛用于促血管生成应用的骨髓驻留干细胞。在体内，它们很可能在骨髓和损伤部位频繁相互作用。在这项研究中，在体外共培养系统中研究了 BM-EPC 和 MSC 之间的物理和生化相互作用，以进一步阐明它们在血管生成中的作用。BM-EPC/MSC 共培养在接种后不久就建立了紧密的细胞-细胞接触，并在 3 天时自我组装形成伸长结构。除了直接接触外，细胞还表现出囊泡运输现象。当共培养在 Matrigel 中时，即使在血清饥饿、生长因子-free 培养基中，管形成也大大增强。MSC 和 BM-EPC 都有助于这些管的形成。然而，共培养中细胞增殖大大减少，并且观察到形态差异。对广泛的血管生成相关转录物的基因表达和聚类分析表明，血管生成标记物上调，但许多其他细胞因子下调。这些数据表明，BM-EPC 和 MSC 之间通过旁分泌和直接细胞接触机制发生串扰，从而调节血管生成反应。
