30 Day Survival Of Orthotopic Cardiac Xenotransplant Of Gtko.htbm.hcd46 Porcine Heart To Nonhuman Primate
Kristopher B. Deatrick, Sunjay Kaushal, MD PhD, Laura DiChiacchio, MD PhD, Bartley Griffith, Muhammad Mohiuddin.
University of Maryland, Baltimore, MD, USA.
Objective(s): Xenotransplantation is a promising source for donor organs for neonates and infants in need of cardiac transplantation. Prolonged survival of a heterotopic genetically-engineered (GE) pig heart is well-established. Here we demonstrate survival of an orthotopic GE heart xenotransplant in a primate recipient beyond the perioperative period.
Methods: The heart from a 10-week-old GE donor pig, with deletion of alpha 1-3 galactosyltransferase (GTKO) and expression of human thrombomodulin (hTBM) and human CD46 (hCD46), was transplanted into a SPF-baboon. Immunosuppression (IS) included anti-CD20 antibody (mAb), anti-thymocyte globulin (ATG), cobra venom factor, and anti-CD40 mAb, followed by anti-CD40 mAb, MMF, and steroids. Graft preservation was achieved with cold Del Nido solution and recipient blood. The total ischemic time was < 40 minutes.
Results: Rapid recovery of heart function and followed reperfusion and was maintained without inotropic support through extubation and recovery with stable hemodynamics. Leukocytes, hemoglobin, platelets, serum chemistries and troponin remained within normal limits. Troponin levels increased in the 3d week and rescue therapy with steroids and anti-CD40 mAb was initiated. The recipient had declining function and was euthanized on day 30. Increasing non-Gal antibody correlated with increasing troponin, though B cell depletion was complete. Histology suggested antibody-mediated rejection.
Conclusions: Survival beyond the peri-operative period can be achieved in orthotopic xenografts. Prolonged survival of GE pig hearts in the working, orthotopic position in a nonhuman primate provides proof of concept of xenotransplantation as viable source of donor organs for young patients, and suggests the need for further research in this area.