Long‐Term Expression of Human Growth Hormone (hGH) in Mice Containing Allogeneic Yolk Sac Cell Derived Neovascular Implants Expressing hGH

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Abstract
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 isotype 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.