gms | German Medical Science

44. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen e. V. (DGPRÄC), 18. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen e. V. (VDÄPC)

12.09. - 14.09.2013, Münster

Extracorporeal human blood perfusion of CD46 & HLA-E double transgenic pig limbs: A technique for the study of immunologic effects in composite tissue xenografts

Meeting Abstract

  • presenting/speaker David Kiermeir - University Hospital Bern, Department of Plastic and Hand Surgery, Bern, Schweiz
  • Esther Vögelin - University Hospital Bern, Department of Plastic and Hand Surgery, Bern, Schweiz
  • Anjan Bongoni - University of Bern, Department of Clinical Research, Bern, Schweiz
  • Andrea Bähr - Ludwig-Maximilian University, Institute of Molecular Animal Breeding and Biotechnology, Munich, Deutschland
  • Hansjörg Jenny - University Hospital, Bern, Department of Cardiovascular Surgery, Bern, Serbien
  • Amandine Pradier - University Hospital and Medical Faculty, Department of Immunology and Allergology, Geneva, Schweiz
  • Anne-Laure Millard - University Hospital and Medical Faculty, Department of Immunology and Allergology, Geneva, Schweiz
  • Mårten Schneider - University Hospital and Medical Faculty, Department of Immunology and Allergology, Geneva, Schweiz
  • David Ayares - Revivicor, Inc, Blacksburg, Virginia, USA
  • Nikolai Klymiuk - Ludwig-Maximilian University, Institute of Molecular Animal Breeding and Biotechnology, Munich, Deutschland
  • Robert Rieben - University of Bern, Department of Clinical Research, Bern, Schweiz
  • Mihai Constantinescu - University Hospital, Bern, Department of Plastic and Hand Surgery, Bern, Deutschland

Deutsche Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen. Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen. 44. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 17. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC). Münster, 12.-14.09.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocFV 84

doi: 10.3205/13dgpraec091, urn:nbn:de:0183-13dgpraec0913

Veröffentlicht: 10. September 2013

© 2013 Kiermeir et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: With increasing demand and limited availability of organ donors xenotransplantation of organs becomes a promising approach. Xenotransplantation of composite tissues would provide a large pool of available tissue for reconstructive surgery without donor site morbidity. Multiple transgene strategies are currently used to overcome rejection of pig-to-human xenografts. In a new founder line, overexpression of human CD46 and HLA-E was combined to prevent complement activation and NK cell reactivity.

Aim: To assess the feasibility of extracorporeal human blood perfusion of porcine composite tissue grafts and to study first immunologic reactions in a pig-to-human xenotransplantation setting.

Methods: 8 forelimbs (4 wildtype and 4 HLA-E/CD46 transgenic) were extracorporeally perfused with whole, heparin-anticoagulated human blood with a pediatric heart-lung machine for 12h and compared to the respective autologous perfusions (n=8). Blood gas analysis probes were collected and hemodynamic parameters monitored hourly. Muscular function was assessed by motor response on direct neural stimulation. Compartment pressure was measured before and after perfusion.

Results: No signs of hyperacute rejection were observed in this model and all limb perfusions could be performed continuously for 12h. Blood gas analysis showed constant physiologic potassium, lactate and pH values in both transgenic and wildtype animals. A statistical significant difference between human blood perfusion in wildtype (w) and transgenic (t) limbs could be detected assessing pH (w: 7.32±0.06; t: 7.35±0.025; p=0.043) and lactate (w: 10.78±0.63; t: 7.11±0.47; p=0.003) whereas no statistical significant differences were observed in potassium and hemoglobin values. In all autologous perfusions, no statistical difference was found in blood gas parameters. Stable and physiologic hemodynamic perfusion parameters (pressure, flow) could be maintained throughout all limb perfusions underlining the good perfusion quality without significant differences between human blood and autologous perfusions in both transgenic and wildtype animals. All limbs showed full muscular response on neural stimulation throughout the experiment in all perfusion groups. Compartment pressures were all within the normal range at the end of the perfusions.

Conclusion: The extracorporeal human blood perfusion of transgenic and wildtype pig limbs is feasible for at least 12 hours and does not cause hyperacute rejection and allows the detailed study of early immunologic effects in xenotransplantation.