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Worldwide First Suc...
Worldwide First Successful and Reproducable Long-Term Survival up to Half a Year : Completed Preclinical Study with Life-Supporting Orthotopic Pig-to-Baboon Cardiac Xenotransplantation (oXHTx) Fullfilling the ISHLT Prerequisite for Clinical Cardiac Xenotransplantation
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- Brenner, P. (författare)
- Ludwig-Maximilian University of Munich
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- Reichart, B. (författare)
- Ludwig-Maximilian University of Munich
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- Laengin, M. (författare)
- Ludwig-Maximilian University of Munich
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- Michel, S. (författare)
- Ludwig-Maximilian University of Munich
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- Buchholz, S. (författare)
- Ludwig-Maximilian University of Munich
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- Dashkevich, A. (författare)
- Ludwig-Maximilian University of Munich
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- Wolf, E. (författare)
- Ludwig-Maximilian University of Munich
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- Reimann, K. (författare)
- MassBiologics
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- Ayares, D. (författare)
- Revivicor, Inc
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- Hagl, C. (författare)
- Ludwig-Maximilian University of Munich
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- Steen, S. (författare)
- Lund University,Lunds universitet,Hjärt- och lungtransplantation,Forskargrupper vid Lunds universitet,Heart and Lung transplantation,Lund University Research Groups
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- Abicht, J. (författare)
- Ludwig-Maximilian University of Munich
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- Engelska 1 s.
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Ingår i: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - : Elsevier BV. - 1557-3117. ; 39:4, s. 12-12
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- PURPOSE: Major hurdles in oXHTx are the delayed xenograft rejection, the early perioperative cardiac xenograft dysfunction (PCXD) and the pig heart overgrowth, which were solved in this study with a costimulation blockade, a new non-ischemic cold preservation and a growth inhibition by anti-proliferative drugs. Aim was to achieve a 90-days-survival of minimal 60% (6 of 10 baboons) in this life-supporting orthotopic pig-to-baboon model (oXHTx), because this is the recommendation of the ISHLT to begin a clinical cardiac XT program. METHODS: We transplanted 8 GalKO/hCD46/hTM transgenic (tg) pig hearts orthotopically into baboons with using a basic immunosuppression consisting of ATG, rituximab, mycophenolate (MMF), cortisone and a costimulation blockade CD40mAb (high dose: 50 mg/kg). To prevent PCXD, we used instead of the crystalloid solution a new non-ischemic 8°C cold perfusion technique with oxygenated erythrocytes. Additional antihypertensive drugs and an mTOR inhibitor (temsirolimus) were applied to inhibit pig xenograft growth and hypertrophy. RESULTS: In comparison to our previous group with crystalloid cardioplegia (Längin et al. Nature. 2018;564:430-433) in this group with cold perfusion preservation (non-ischemic) no PCXD was found. One baboon died of a pancreatitis on day 14, another of sepsis on day 26. By using the antiproliferative therapy, 6 of 8 recipient baboons reached the end of study, were long-term surviving (4 were actively terminated after 90 days according to the guidelines of our government). With special permit two further experiments could be prolonged to half a year and the animals were terminated on day 182 and 195. All baboons lived under excellent physical conditions and no hyperacute rejection or DXR occurred. CONCLUSION: First time in a life-supporting oXHT of multi-tg pig hearts here was a consistent reproduceable long-term survival of 3 - 6 months achieved, which is a major progress after 25 years of research. This is an essential milestone and breakthrough and meets the prerequisite according to the ISHLT to begin a clinical phase I study with patients in terminal heart failure. This paves the way to clinical cardiac XT in the next 2 to 5 years.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
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Till lärosätets databas
- Av författaren/redakt...
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Brenner, P.
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Reichart, B.
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Laengin, M.
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Michel, S.
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Buchholz, S.
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Dashkevich, A.
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visa fler...
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Wolf, E.
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Reimann, K.
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Ayares, D.
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Hagl, C.
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Steen, S.
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Abicht, J.
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och Kardiologi
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Lunds universitet