Scaffold Composition Determines the Angiogenic Outcome of Cell-Based Vascular Endothelial Growth Factor Expression by Modulating Its Microenvironmental Distribution
Scaffold Composition Determines the Angiogenic Outcome of Cell-Based Vascular Endothelial Growth Factor Expression by Modulating Its Microenvironmental Distribution
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DOI：
10.1002/adhm.201700600
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发表时间：
2017-12-20
影响因子：
10
通讯作者：
Marsano, Anna
中科院分区：
文献类型：
--
作者：
Gaudiello, Emanuele;Melly, Ludovic;Marsano, Anna
递送过表达血管内皮生长因子（VEGF）的遗传修饰细胞是诱导缺血组织中的治疗性血管生成的有前途的方法。蛋白质的作用受到其与细胞外基质组分相互作用的严格调节。其治疗潜力取决于在微环境水平上持续但受控的释放，以避免形成异常血管。在这项研究中，假设支架的组成在调节3D细胞构建体释放的VEGF的结合，从而调节其治疗效果中起关键作用。据发现，胶原海绵，其结合VEGF差，防止形成局部热点的浓度过高，因此，排除异常血管生成的发展，尽管不受控制的表达由基因工程群体的脂肪组织来源的基质细胞。相反，在VEGF结合蛋白支架上接种后，相同的细胞群在14天后引起异常扩大的血管结构。在大鼠模型中，基于胶原的工程组织还在补片本身和下层心肌中诱导安全有效的血管生成。这些发现开辟了新的观点的控制和交付的促血管生成的刺激，是基本的血管化的工程组织/器官。
Delivery of genetically modified cells overexpressing Vascular Endothelial Growth Factor (VEGF) is a promising approach to induce therapeutic angiogenesis in ischemic tissues. The effect of the protein is strictly modulated by its interaction with the components of the extracellular matrix. Its therapeutic potential depends on a sustained but controlled release at the microenvironmental level in order to avoid the formation of abnormal blood vessels. In this study, it is hypothesized that the composition of the scaffold plays a key role in modulating the binding, hence the therapeutic effect, of the VEGF released by 3D-cell constructs. It is found that collagen sponges, which poorly bind VEGF, prevent the formation of localized hot spots of excessive concentration, therefore, precluding the development of aberrant angiogenesis despite uncontrolled expression by a genetically engineered population of adipose tissue-derived stromal cells. On the contrary, after seeding on VEGF-binding egg-white scaffolds, the same cell population caused aberrantly enlarged vascular structures after 14 d. Collagen-based engineered tissues also induced a safe and efficient angiogenesis in both the patch itself and the underlying myocardium in rat models. These findings open new perspectives on the control and the delivery of proangiogenic stimuli, and are fundamental for the vascularization of engineered tissues/organs.