Cardiac xenotransplantation from 10 gene-modified pig hearts into non-human primates
Avneesh Singh1, Corbin. E Goerlich1, Tianshu Zhang1, Gheorghe Braileanu1, Alena Hershfeld1, Ivan Tatarov1, Billeta Lewis1, Faith Sentz1, Sarah Mudd1, Cinthia B Drachenberg3, David Ayares3, Bartley Griffith1, Muhammad M Mohiuddin1.
1Surgery, School of Medicine, University of Maryland, Baltimore, MD, United States; 2Pathology, School of Medicine, University of Maryland, Baltimore, MD, United States; 3Revivicor Inc, Blacksburg, VA, VA, United States
Multi-genes modifications in donor pig hearts have significantly prevented early xenograft rejection and improved cardiac xenograft survival. Earlier, we reported nine-month survival of orthotopic (life-sustaining) multi-gene edited pig hearts in baboons using the non-ischemic cardiac preservation (NICP) technique and anti-CD40-monoclonal antibody-based co-stimulation blockade. In this study, we have tested "10 genes" edited donor pig heart transplantation in baboons. The cardiac xenograft survival of 10 gene-edited hearts in baboons (n=4) was 128±36 days Mean ± SE), and the longest survival was 225 days, less than previously reported survival with 7 gene-edited pig hearts for nine months. Adipose tissue (Fat) deposition, chronic vasculopathy, micro and macro thrombosis, and acute cellular rejection were seen in explanted cardiac xenograft. Our results indicate the suitability of 10 gene pigs for xenotransplant experiments in the NHP model despite shorter graft survival.
