MORPHOLOGY OF HDAF (CD55) TRANSGENIC PIG KIDNEYS FOLLOWING EX-VIVO HEMOPERFUSION WITH HUMAN BLOOD

Discordant xenotransplantation of pig kidneys into man may be possible in the future using transgenic organs which regulate complement activ ity. It was the aim of this experimental study to characterize morphol ogic alterations of organs transgenic for human decay accelerating fac tor (hDAF/CD55) perfused with human blood since no data on function of these organs after exposure to human blood are available. An exvivo s ystem was developed that allows computer driven pressure-controlled pe rfusion of kidneys including a separate cartridge oxygenator circuit. Following cold ischemia time of 1-4 hr, 8 kidneys from heterozygote tr ansgenic animals (TG) and 9 control kidneys (C) were perfused with 500 ml freshly drawn heparinized human blood at physiological conditions. A histologic grading system from 0 to +4 was used to describe the his tologic findings. Using a mouse antihuman DAF moAB, hDAF was stained o n all TG kidneys both on glomerular capillary (4+) and vascular endoth elium (2+), but there was no detectable hDAF-expression on controls. N o difference in xenoantibody deposition on vascular endothelium was se en between both groups. There was comparable staining for complement f raction C4 in both groups, but significant reduction of C3 and C9 stai ning on glomerular and vascular endothelium in TG. P-selectin was expr essed on a higher level in C (+4) compared with TG (+2). Neutrophil ex travasation [NP-57 elastase] was higher in C (80.2 vs. 32.2 C vs. TG [ values as n/high power field]). Tubular epithelial cell swelling and m ild necrosis was paralleled by glomerular hemorrhage and platelet micr othrombus formation in both groups as seen in transmission electron mi croscopy. The observed results allow the conclusion that hDAF expressi on on transgenic pig kidneys was sufficient to inhibit complement acti vation beyond C3 during xenoperfusion with human blood despite xenoant ibody deposition.