The Case for Pig Heart Xenotransplantation in Infants with Complex Congenital Heart Disease

Abstract

Purpose There is a lack of human heart allografts for transplantation (Tx) in infants with life-threatening congenital defects. Staged palliation is less than optimal. Grafts from deceased human donors will never solve the problem of organ supply. XenoTx, using genetically-engineered (GE) pigs as sources of hearts is a potential option. Today, survival of GE pig organs in immunosuppressed nonhuman primates is being measured in months or even years. We have therefore begun to explore the possibility of pig heart Tx in neonates and infants. Methods We measured (1) serum antibody levels in infants (n=50), children (n=20), and adults (n=14 to WT; n=64 to TKO) to red blood cells (RBCs) from wild-type (WT, i.e., genetically unmodified), and TKO (i.e., not expressing any of the 3 known pig xenoantigens) pigs (from Revivicor); (2) anti-pig antibody levels in infants and children (n=20) who had undergone previous cardiac surgery with implantation of porcine/bovine tissue grafts, to determine whether they had become sensitized to pig antigens; and (3) anti-pig antibodies in one infant who had undergone previous cardiac surgery and had become highly sensitized to HLA, to determine whether sensitization to pig antigens had developed. Results (1) Some infants had IgM (52%) and/or IgG (76%) antibodies against WT pRBCs. All children and adults had anti-WT pig IgM/IgG antibodies. In contrast, only 1 infant, 5% of children (1/20) and 5% of adults (3/64) had anti-TKO IgM/IgG antibodies, and in all cases the level was very low. (2) One infant exposed previously to porcine/bovine tissue had minimal IgM/IgG to TKO pRBCs. (3) The one highly HLA-sensitized infant had no antibodies to TKO pig antigens (or to swine leukocyte antigens). Conclusion The Tx of a TKO pig heart could be carried out in most infants in the absence of anti-pig antibodies, indicating no or minimal risk of antibody-mediated rejection. Neither previous cardiac surgery (even if the patient became sensitized to HLA) nor previous exposure to porcine or bovine antigens should be detrimental to subsequent TKO pig heart Tx. We suggest a TKO pig heart could provide a successful bridge to alloTx in infants. (Sensitization to pig cells is not detrimental to subsequent alloTx.)