Wei Y, Li J, Wagner T E
Edison Biotechnology Institute, Molecular and Cellular Biology Program, Ohio University, Athens, USA.
Stem Cells. 1996 Mar;14(2):232-8. doi: 10.1002/stem.140232.
We have established a systemic gene delivery animal model system by using cultured murine embryonic yolk sac cells, which can be easily genetically modified in vitro and participate in angiogenesis in vivo when basement membrane proteins (Matrigel) are provided in syngeneic mice. In the present study, we successfully applied this system to allogeneic mice. In order to suppress donor cell-specific immune responses, the costimulatory signal transduction pathway of T cell activation was blocked by treating the recipient allogeneic C57BL/6 mice with rat-antimouse B7.2 antibody. As a result of this suppression, human growth hormone, the therapeutic gene product, could be detected for over 340 days, while it could only be detected in mice treated with rat-IgG2a, the iso-type control of anti-B7.2, for fewer than 50 days. This is the first ex vivo gene delivery system that can express a therapeutic gene product, long-term, in an allogeneic host.
我们利用培养的小鼠胚胎卵黄囊细胞建立了一个系统性基因递送动物模型系统，该细胞在体外可轻松进行基因改造，并且当在同基因小鼠中提供基底膜蛋白（基质胶）时，能在体内参与血管生成。在本研究中，我们成功地将此系统应用于异基因小鼠。为了抑制供体细胞特异性免疫反应，通过用大鼠抗小鼠B7.2抗体处理受体异基因C57BL/6小鼠，阻断了T细胞激活的共刺激信号转导途径。由于这种抑制作用，治疗性基因产物人类生长激素在超过340天的时间里都能被检测到，而在使用大鼠IgG2a（抗B7.2的同型对照）处理的小鼠中，该产物只能在不到50天的时间里被检测到。这是首个能在异基因宿主中长期表达治疗性基因产物的体外基因递送系统。
