Combination of hDAF-transgenic pig hearts and immunoadsorption in heterotopic xenotransplantation of immunosuppressed baboons

Brenner, Paolo; Schmoeckel, Michael; Reichenspurner, Hermann; Wimmer, Cornelius; Rucker, A.; Eder, V.; Uchita, S; Brandl, Ulrike; Felbinger, Thomas W.; Meiser, B; Hammer, C.; Reichart, Bruno

doi:10.1055/s-2006-925863

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Central pontine myelinolysis related to fast sodium shifts (day 7) and severe features of peritonitis on day 3 were non‐cardiac reasons for euthanasia (experiments 16 and 20, Table ). Median survival in this group 2, omitting the non‐informative experiments 12 to 14 and 16, 20, was 16 days; there was no significant difference in survival between group 1 and group 2 (Table , Fig. ).…”

Section: Resultsmentioning

confidence: 82%

See 1 more Smart Citation

Pre‐clinical heterotopic intrathoracic heart xenotransplantation: a possibly useful clinical technique

Abicht

Mayr

Reichart³

et al. 2015

Xenotransplantation

View full text Add to dashboard Cite

Background: As a step towards clinical cardiac xenotransplantation, our experimental heterotopic intrathoracic xenotransplantation model offers a beating and ejecting donor heart while retaining the recipient 0 s native organ as a backup in case of graft failure. Clinically applicable immunosuppressive regimens (IS) were investigated first, then treatments known to be effective in hypersensitized patients or those with recalcitrant rejection reactions. Methods: Consecutive experiments were carried out between 2009 and 2013. Twenty-one genetically modified pigs (GGTA1-knockout/hCD46/ AE thrombomodulin, in one case HLA-E instead) were used as donors. In all experiments, two cycles of immunoabsorption reduced preformed antibodies. Recipient baboons were divided into two groups according to IS regimen: In group one (n = 10), pre-treatment started either one (anti-CD20) or four weeks (anti-CD20 plus the proteasome inhibitor bortezomib) prior to transplantation. The extended conventional (as for allotransplantation) immunosuppressive maintenance regimen included anti-thymocyte globuline, tacrolimus, mycophenolate mofetil, methylprednisolone and weekly anti-CD20. In group two (n = 11), myeloablative pre-treatment as in multiple myeloma patients (long and short regimens) was added to extended conventional IS; postoperative total thoracic and abdominal lymphoid irradiation (TLI; single dose of 600 cGY) was used to further reduce antibody-producing cells. Results: In the perioperative course, the surgical technique was safely applied: 19 baboons were weaned off extracorporeal circulation and 17 extubated. Nine animals were lost in the early postoperative course due to causes unrelated to surgical technique or IS regimen. Excluding these early failures, median graft survival times of group 1 and 2 were 18.5 (12-50) days and 16 (7-35) days. Necropsy examination of group 1 donor organs revealed hypertrophy of the left ventricular wall in the six longer-lasting grafts; myocardial histology confirmed preclinical suspicion of humoral rejection, which was not inhibited by the extended conventional IS including intensified treatments, and signs of thrombotic microangiopathy. Grafts of group 2 presented with only mild-to-moderate features of humoral rejection and thrombotic microangiopathy, except in one case of delayed rejection on day 17. The other experiments in this group were Jan-Michael Abicht, terminated because of untreatable pulmonary oedema, recurring ventricular fibrillation, Aspergillus sepsis, as well as a combination of a large donor organ and late toxic side effects due to TLI. Conclusions: Longer-term results were difficult to achieve in this model due to the IS regimens used. However, we conclude that heterotopic intrathoracic heart transplantation may be an option for clinical xenotransplantation.

show abstract

Section: Resultsmentioning

confidence: 82%

“…In both groups, all immunoglobulins type G (IgG) subclasses as well as immunoglobulins type M (IgM) (likewise type A and E) were reduced by two immunoadsorption treatments (IA, TheraSorb ™ ‐Ig flex Adsorber and Life 18, Miltenyi, Biotec, Bergisch‐Gladbach, Germany) on day ‐2 and immediately before Tx .…”

Section: Methodsmentioning

confidence: 99%