Hearts from transgenic pigs constructed with CD59/DAF genomic clones demonstrate improved survival in primates

We have previously created transgenic pigs bearing the human complement reg ulatory proteins CD59 and decay-accelerating factor (DAF) by either the int ercellular transfer or the cDNA transgenic method. To achieve more physiolo gic protein expression, we constructed a new line of transgenic pigs with C D59 and DAF human genomic clones. We transplanted these CD59/DAF transgenic pig hearts into baboons immunosuppressed with cyclosporine, methylpredniso ne or leflunomide/mofetil mycophenolate. The four wild-type hearts survived for 20-80 min, whereas the four CD59/DAF hearts functioned for 85-130 h. I mmunohistochemical staining showed levels of CD59 and DAF protein expressio n similar to that in human hearts. Wild-type and transgenic hearts demonstr ate a similar level of IgM deposition, although transgenic hearts suffered less hyperacute rejection and thus less membrane attack complex deposition. The histology of the transgenic grafts after explant was consistent with a cute vascular rejection, with a high level of IgG deposit compared with wil d-type control. We conclude that this new line of CD59/DAF transgenic pigs express high levels of the transgene products, which conferred longer survi val because of better protection from hyperacute rejection. Similar to prev ious transgenic pigs, however, these animals suffered from delayed xenograf t rejection.