Prolonged survival of GalT-KO swine skin on baboons

Abstract

Background: Allogeneic skin is currently the best alternative to autologous skin as a temporary treatment for severe burns, but it has several drawbacks. As a potential alternative, we have evaluated GalT-KO swine skin, which lacks expression of the Gal epitope, to investigate the effect of eliminating this epitope on survival of pig-to-baboon skin grafts.

Methods: Two adult baboons that had fully recovered from previous T cell depletion received simultaneous skin grafts from: (i) GalT-KO swine, (ii) Gal-positive swine, (iii) a third-party baboon, and (iv) self (control skin). Recipients were treated with cyclosporin for 12 days and the survival, gross appearance, and histology of the grafts were compared.

Results: In both baboons, the GalT-KO skin survived longer than either the Gal-positive swine skin or the allogeneic skin. Early rejection of the Gal-positive skin appeared to be mediated by cytotoxic preformed anti-Gal IgM antibodies, while the rejection of GalT-KO skin appeared to result from cellular mechanisms.

Conclusions: GalT-KO skin may have potential clinical benefits as an alternative to allogeneic skin as a temporary treatment for severe skin injuries.

Fig. 1

(A) Baboon 1 skin grafts on days 0 and 4 (from left to right): self, GalT-KO, Gal-positive, allogeneic baboon. (B) Baboon 2 skin grafts on days 0 and 7 (from left to right): self, GalT-KO, Gal-positive, and allogeneic baboon.

Fig. 2

Histology of skin grafts on baboon 1, biopsies on days 0, 4, and 7.

Fig. 3

Antibody-complement mediated cytotoxicity assay of sera from baboons 1 (A) and 2 (B) at 1 : 4 dilution showed increased antibody-mediated cytotoxicity after day 4, with higher baseline killing levels against Gal-positive cells than against GalT-KO cells. Addition of DTT demonstrated that early cytotoxicity was largely due to preformed anti-Gal IgM (solid black line = Gal-positive cell targets without DTT, solid gray line = GalT-KO cell targets without DTT, dashed black line = Gal-positive cell targets with DTT).

Fig. 4

Immunohistochemistry of Gal-positive (A,C) and GalT-KO (B,D) skin on baboons 1 (POD 7) and 2 (POD4) showing early deposition of anti-Gal IgM but not anti-non-Gal IgM.