Stand der Technik und Durchbruch bei der kardialen Xenotransplantation. Schweineherzen als alternative Lösung des Spenderorganmangels

Brenner, Paolo (2022): Stand der Technik und Durchbruch bei der kardialen Xenotransplantation. Schweineherzen als alternative Lösung des Spenderorganmangels. In: Zeitschrift für Herz-, Thorax- und Gefässchirurgie, Bd. 36, Nr. 5: S. 334-354

Abstract

AIM According to the ISHLT advisory board guidelines for xenotransplantation (XT) a 90-day survival of a minimal 60 % (6 of 10 baboons) in a life-supporting orthotopic pig-to-baboon model (oXHTx) is recommended as a prerequisite to begin a clinical cardiac XT program. The Munich xenotransplantation research team around Prof. Paolo Brenner and Prof. Bruno Reichart reproduced a previous excellent survival of 945 days in a non-life-supporting abdominal model now in a life-supporting orthotopic model with the same CD40mAb costimulation blockade immunosuppression (IS). Methods In the Munich team oXHTx in baboons with GalKO/hCD46/hTM transgenic (tg) pig hearts was performed using a basic IS consisting of ATG, rituximab, MMF, cortisone and CD40mAb. To avoid early perioperative cardiac xenograft dysfunction (PCXD) as a kind of early cardiac low output, we replaced the crystalloid cardioplegia with a non-ischemic 8 celcius cold perfusion solution with oxygenated erythrocytes. To prevent pig xenograft overgrowth and hypertrophy, antihypertensive drugs and an anti-proliferative mTOR inhibitor (temsirolimus) were used. Results In comparison to crystalloid cardioplegia, now with non-ischemic cold perfusion no PCXD was found. With successful treatment of xenograft (over)growth and hypertrophy, 6 recipient baboons were long-term surviving (4 were actively terminated after 90 days according to the guidelines of the government). Two further experiments could be prolonged up to 182 and 195 days. All baboons lived under excellent physical conditions with no hyperacute or delayed xenograft rejection. Discussion Within the last 3 years after 25 years of experimental research in oXHT now we achieved a major progress and the essential milestone and breakthrough by realizing a constantly reproducible long-term survival of 3-6 months. Now the prerequisite according to the ISHLT for beginning a clinical phase I study are fulfilled and paves the way to clinical cardiac XT in the next 2-5 years.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0930-9225
• Sprache: Deutsch