Squinto S P, Madri J A, Kennedy S, Springhorn J
Alexion Pharmaceuticals, Inc, New Haven, CT 06511, USA.
In Vivo. 1994 Nov-Dec;8(5):771-80.
A wide variety of somatic cells are being explored for the introduction of foreign genes with a view toward gene therapy. A prime requirement for successful gene therapy is the sustained expression, effective dosing, and systemic delivery of the therapeutic gene product. Microvascular endothelial cells offer several advantages over other cell types as a somatic cell gene delivery vehicle in that they provide direct secretion of protein into the blood stream and they are amendable to highly stable retroviral-based protein expression. Importantly, they also offer a large surface volume to size ratio in that they can be induced with angiogenic factors to form organized capillary-like structures in vitro when grown in a three dimensional culture system using collagen gels. These genetically-modified capillary endothelial cells (the ENCEL system) maintained in collagen gels can be stably transplanted and removed. The unique biological properties of microvascular capillary endothelial cells allows the ENCEL system to provide large numbers of cells in a small volume which offers the highly desired opportunity for providing a sustained and effective dose of a therapeutic protein. Alexion is currently applying its Unigraft immunotherapeutic and engineering technologies to commercialize a non-human ENCEL system acceptable for implantation into any patient.
为了基因治疗，人们正在探索各种各样的体细胞来导入外源基因。成功进行基因治疗的一个主要要求是治疗性基因产物的持续表达、有效给药和全身递送。微血管内皮细胞作为体细胞基因递送载体，比其他细胞类型具有几个优势，因为它们能将蛋白质直接分泌到血流中，并且适合基于逆转录病毒的高度稳定的蛋白质表达。重要的是，它们还具有较大的表面积与体积比，因为当在使用胶原蛋白凝胶的三维培养系统中生长时，它们可以被血管生成因子诱导在体外形成有组织的毛细血管样结构。维持在胶原蛋白凝胶中的这些基因修饰的毛细血管内皮细胞（ENCEL系统）可以稳定移植和移除。微血管内皮细胞独特的生物学特性使ENCEL系统能够在小体积内提供大量细胞，这为提供持续有效的治疗性蛋白质剂量提供了非常理想的机会。Alexion公司目前正在应用其Unigraft免疫治疗和工程技术，将一种可植入任何患者体内的非人ENCEL系统商业化。
