First experience with heterotopic thoracic pig-to-baboon cardiac xenotransplantation

Bauer, Andreas; Postrach, J.; Thormann, Michael; Blanck, S.; Faber, Claudius; Wintersperger, Bernd J.; Michel, Sebastian; Abicht, Jan‐Michael; Christ, F.; Schmitz, Christoph; Schmoeckel, Michael; Reichart, Bruno; Brenner, Paolo

doi:10.1111/j.1399-3089.2010.00587.x

Cited by 42 publications

(36 citation statements)

References 9 publications

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“…Numerous other pig-to-nonhuman-primate transplantations have been performed, and no transmission of PERV was observed (Table 8). In addition, in heterotopic thoracic pigto-baboon cardiac xenotransplantation (15), no PERV transmission was observed using a Western blot assay to detect PERVspecific antibodies (Denner et al, unpublished data).…”

Section: Pervsmentioning

confidence: 99%

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

2012

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SUMMARY Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Infection of ecotropic PERV-C is limited to pig cells. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Like all retroviruses, they may induce tumors and/or immunodeficiencies. To date, all experimental, preclinical, and clinical xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference.

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Section: Pervsmentioning

confidence: 99%

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

2012

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“…As xenogeneic transplantation could potentially solve the organ shortage in cardiac transplantation, special interest lies in overcoming the mechanisms of xenograft rejection [2,3]. Several innovations, like genetically modified donor animals [14], achieved increased long-term survival in preclinical xenotransplantation models [15,16,17]. Yet, cardiac xenotransplantation is still far from being established clinically [18].…”

Section: Discussionmentioning

confidence: 99%

The Coronary Microcirculation in Hamster-to-Rat Cardiac Xenografts

Geiger

Buchholz²,

Michel³

et al. 2015

Eur Surg Res

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Background: The aim of this study was to establish a new experimental model to directly analyse the coronary microcirculation in cardiac xenografts. Methods: Intravital fluorescence microscopy (IVM) of the subepicardial microcirculation in heterotopically transplanted hamster-to-rat cardiac xenografts was performed at 30 and 90 min of reperfusion. We quantitatively assessed the microcirculatory perfusion characteristics as well as the interactions of leukocytes and platelets with the endothelium of postcapillary coronary venules in non-sensitised as well as sensitised recipients. Results: In this first experimental IVM study of cardiac xenografts, we successfully visualised the subepicardial microcirculation, i.e. feeding arterioles, nutritive capillaries and draining postcapillary venules, during reperfusion. Leukocyte-endothelial and platelet-endothelial cell interactions could be quantified. In the non-sensitised group, the myocardial microcirculation remained stable during the observation period of 90 min, whereas in the sensitised group, xenografts were rejected immediately. Conclusions: We established a model for the assessment of the microcirculatory dysfunction and inflammation during ischaemia/reperfusion injury in hamster-to-rat cardiac xenografts.

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“…The group from Munich, Germany, has achieved so far 50 days of survival in a genetically modified animal model with the unique thoracic heterotopic heart transplantation technique developed by Barnard and Losman [33,34], using a dedicated immunosuppressive treatment described above [29 & ]. Before the step into the clinic can be made, the guidelines of the Xenotransplantation ISHLT Advisory Board [35] need to be followed achieving good graft function for a minimum of 3 months in a lifesupporting position in at least 60% of consecutive experiments.…”

Section: Xenotransplantationmentioning

confidence: 99%