Department of Anaesthesiology
Walter-Brendel-Centre - LMU Munich
Histological findings in a heterotopic thoracic pig-to-baboon cardiac xenotransplantation model
Tanja Mayr1,3, Isabelle Lutzmann1,3, Sonja Guethoff1,3, Martin Langenmayer4, Eckhard Wolf5, David Ayares6, Bruno Reichart3, Paolo Brenner1,3, Jan-Michael Abicht2,3.
1Department of Cardiac Surgery, Ludwig-Maximilians University, Munich, Germany; 2Department of Anaesthesiology, Ludwig-Maximilians University, Munich, Germany; 3Walter-Brendel-Centre, Ludwig-Maximilians University, Munich, Germany; 4Department of Veterinary Pathology, Ludwig-Maximilians University, Munich, Germany; 5Department of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians University, Munich, Germany; 6Revivicor Inc., Blacksburg, VA, United States
Introduction: Histological evaluations at the endpoints of the graft and the recipient organ in a heterotopic thoracic cardiac xenotransplantation (working heart) model.
Methods: 23 heterotopic thoracic pig-to-baboon cardiac xenotransplantations (Gal-KO/hCD46/± hTM respectively ± HLA-E genetically modified pigs) were subdivided into 3 groups according to the immunosuppression (IS) used: A (n=10) IS as for allotransplantations (including ATG, MMF, tacrolimus and steroids), B (n=11), total thoracic and abdominal lymphoid irradiation, C (n=2) costimulation blockade with CD40 antibody. All recipients had also pretreatment and basic IS. Recipient hearts (n=23) were also investigated. Histology included: hematoxylin-eosin stains using the histologic injury severity score (HISS; min. = 0, max. = 27); particular parameters were perivascular edema, erythrocyte extravasation, leucocyte recruitment, intraluminal thrombi, hypereosinophilia, nuclear changes, necrosis, cell infiltration and the presence of granulation tissue. Additional immunohistochemical analyses comprised depositions of IgM, C4d, fibrin, C1q and CD45.
Results: The mean graft survival was 14.5 ± 14.9 days in group A, 11.4 ± 10.7 days in group B and 13 respectively 35 days in group C. There was no correlation between graft survival and HISS score in any of the groups. In contradistinction, HISS score was significantly different when comparing the various IS treatments: p=0.01, A vs. B; p=0.003, B vs. group C. The two parameters “nuclear changes” and “necrosis” were notably different but not statistically significant. Immunohistochemical evaluations indicated that there was less IgM deposition in group B compared to groups A and C. CD45 positive B-cells were found less in groups B and C when compared to A.
Little damage was found in the recipient hearts but more in the right than in the left ventricles.
Conclusion: Regarding the IS regimens used, we saw histologic differences within the donor organs. Cardiac damage to the right ventricle of the recipient was minimal.
15:30 - 17:00
|Solid Organ Xenotransplantation (1)||Histological findings in a heterotopic thoracic pig-to-baboon cardiac xenotransplantation model||Room 109|
15:30 - 17:00
|Solid Organ Xenotransplantation (1)||Different immunosuppressive regimens in preclinical, discordant xenogeneic, heterotopic thoracic pig-to-baboon heart transplantations||Room 109|