Vallbacka Jennifer J, Sefton Michael V
Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9.
Tissue Eng. 2007 Sep;13(9):2259-69. doi: 10.1089/ten.2006.0284.
Vascularization caused by encapsulated cells engineered to secrete vascular endothelial growth factor (VEGF) improved the in vivo survival of the encapsulated cells in a syngeneic mouse Matrigel plug model. Murine fibroblast cells (L929) were engineered to secrete recombinant human vascular endothelial growth factor (rhVEGF(165)). Transfected and nontransfected L929 cells were microencapsulated in a 75:25 hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA) copolymer. Capsules containing transfected cells induced vascularization in vivo at 1 and 3 weeks postimplantation. In histological sections, a significant positive correlation was seen between the number of capsules and blood vessel density for VEGF-secreting cell capsule implants. New vessels, many positively stained for smooth muscle cells and pericytes, were seen surrounding these VEGF-secreting cell capsule explants. Few vessels were seen in nontransfected L929 capsule implants. The viability of transfected and nontransfected encapsulated cells was assessed on explantation. Although the viability of all encapsulated cells decreased at both 1 and 3 weeks, encapsulated VEGF-secreting cells retained more of the viability than did encapsulated nontransfected control cells. Genetically modified cells promoted vascularization in this context and appeared to enhance the viability of the encapsulated cells, although the extent of the functional benefit was less than expected. Additional effort is required to enhance the benefit, to quantify it, and to understand further the host response to HEMA-MMA microencapsulated cells and tissue constructs, more generally.
经工程改造分泌血管内皮生长因子（VEGF）的封装细胞所引起的血管化，在同基因小鼠基质胶栓模型中提高了封装细胞的体内存活率。将鼠成纤维细胞（L929）进行工程改造以分泌重组人血管内皮生长因子（rhVEGF(165)）。将转染和未转染的L929细胞微封装在75:25的甲基丙烯酸羟乙酯 - 甲基丙烯酸甲酯（HEMA - MMA）共聚物中。含有转染细胞的胶囊在植入后1周和3周时在体内诱导血管化。在组织学切片中，对于分泌VEGF的细胞胶囊植入物，可见胶囊数量与血管密度之间存在显著正相关。在这些分泌VEGF的细胞胶囊外植体周围可见许多新血管，其中许多平滑肌细胞和周细胞呈阳性染色。在未转染的L929胶囊植入物中可见的血管很少。在取出时评估转染和未转染的封装细胞的活力。尽管所有封装细胞的活力在1周和3周时均下降，但分泌VEGF的封装细胞比未转染的封装对照细胞保留了更多的活力。在这种情况下，基因改造细胞促进了血管化，并且似乎提高了封装细胞的活力，尽管功能益处的程度低于预期。需要进一步努力来增强这种益处、对其进行量化，并更全面地进一步了解宿主对HEMA - MMA微封装细胞和组织构建体的反应。
