Life Supporting Orthotopic Cardiac Xenotransplantation Using Multiple Human Gene Expressing Pigs in Non Human Primates
1Department of Surgery, University of Maryland, Baltimore, MD, 2Revivicor Inc, Blacksburg, WV
Meeting: 2022 American Transplant Congress
Abstract number: 84
Keywords: Graft survival, Heart/lung transplantation, Preclinical trails
Topic: Basic Science » Basic Science » 13 - Xenotransplantation
Session Information
Session Time: 3:30pm-5:00pm
Presentation Time: 4:40pm-4:50pm
Location: Hynes Room 302
*Purpose: Cardiac xenotransplantation (CXTx) is proposed as an alternate treatment for end-stage cardiac failure patients. The prolonged survival of a heterotopic genetically engineered (GE) pig heart is well-established. Here we demonstrate the successful life-supporting orthotopic CXTx (OHTx) survival from various GE donor pigs.
*Methods: Orthotopic cardiac xenotransplantation (OHTx) from GE donor pig was performed in a 3-4-year-old baboon (n=10). GE donor pigs were divided into 4 groups based on the gene modifications (Table 1). Immunosuppression consisted of targeted T and B cell depletion along with costimulation blockade with anti-CD40 mAb. Cardioplegia was performed using the combination of DelNido solution or steen solution and recipient blood. A modified Shumway biatrial technique was used to perform heart transplantation. The total average ischemic time was between 90- 120 minutes as the heart was re-perfused after left atrial and aortic anastomoses were completed.
*Results: Life-supporting OHTx was performed successfully and the recipient with GE donor pig heart survived from 30 days to up to 264 days (median 100 days). The use of a heart preservation solution (either blood cardioplegia or Steen solution), minimal ischemic time, and early extubation allowed rapid recovery of heart function in the recipient. The use of a larger baboon (>20Kg) eliminated the requirement of allogeneic blood during or immediately after cardiopulmonary bypass. Though the role of every single gene was not feasible, the additional genetic modifications seem to be helpful
*Conclusions: These experiments demonstrate that OHTx can be achieved beyond the early perioperative period which has previously been reported as a major hurdle in CXTx. The combined effect of multiple gene modifications appears to be helpful in overcoming the various mechanisms of xenograft rejection. Future studies are in progress to evaluate the remaining barriers and achieve longer life-supporting cardiac xenotransplantation.
To cite this abstract in AMA style:
Singh AK, Goerlich C, Zhang T, Tatarov I, Odonkor P, Strauss E, Williams B, Lewis B, Hershfeld A, Sentz F, Ayares D, Kaczorowski D, Griffith B, Mohiuddin M. Life Supporting Orthotopic Cardiac Xenotransplantation Using Multiple Human Gene Expressing Pigs in Non Human Primates [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/life-supporting-orthotopic-cardiac-xenotransplantation-using-multiple-human-gene-expressing-pigs-in-non-human-primates/. Accessed May 6, 2025.« Back to 2022 American Transplant Congress