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.

中文翻译：

---

支架组成通过调节其微环境分布来确定基于细胞的血管内皮生长因子表达的血管生成结果。

传递过表达血管内皮生长因子（VEGF）的基因修饰细胞是一种在缺血性组织中诱导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成分的相互作用的严格调节。其治疗潜力取决于在微环境水平上的持续但受控的释放，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（因此具有治疗作用）中起关键作用。已发现，与VEGF结合较差的胶原蛋白海绵可防止形成浓度过高的局部热点，因此，尽管遗传工程改造的脂肪组织来源的基质细胞表达失控，但仍阻止了异常血管生成的发展。相反，在接种结合VEGF的蛋清支架后，相同的细胞群体在14 d后引起血管结构异常扩大。在大鼠模型中，基于胶原蛋白的工程组织还可以在贴片本身和基础心肌中诱导安全有效的血管生成。这些发现为控制和递送促血管生成的刺激开辟了新的视角，对于工程组织/器官的血管形成至关重要。14 d后，相同的细胞群导致血管结构异常扩大。在大鼠模型中，基于胶原蛋白的工程组织还可以在贴片本身和基础心肌中诱导安全有效的血管生成。这些发现为控制和递送促血管生成的刺激开辟了新的视角，对于工程组织/器官的血管形成至关重要。14 d后，相同的细胞群导致血管结构异常扩大。在大鼠模型中，基于胶原蛋白的工程组织还可以在贴片本身和基础心肌中诱导安全有效的血管生成。这些发现为血管生成刺激的控制和传递开辟了新的视角，并且对工程组织/器官的血管形成至关重要。