Pig-to-non-human primate heart transplantation: The final step toward clinical xenotransplantation?

Clinical xenotransplantation of the heart: At the watershed

“…The xenografts were from pigs with the same or similar genetic modifications as those used by Mohiuddin et al, 6 and the baboons were treated with immunosuppression similar to that of Mohiuddin et al 6 (plus an mammalian target of rapamycin inhibitor to limit myocardial remodeling 7 ). The present report 2 Some might question whether 6 of 8 xenografts functioning 3 months or more well exceeds or meets the ISHLT standard (60% of at least 10 life-supporting xenografts functioning 3 months 4 ). We think giving more than passing mention to this standard formulated more than 15 years before the immunologic barriers had been overcome, obscures the significance of Reichart et al 2 's accomplishment.…”

“…Yet, these advances were countered at every turn by discovery of new antigens, more incompatibilities and longer lists of zoonotic organisms. But in the current issue of Journal of Heart and Lung Transplantation, and in a previous report in another journal, 2,3 Reichart et al 2 report > 3-month survival and function of orthotopic pig cardiac xenografts in baboons given clinically acceptable immunosuppression. The results "fulfill for the first time the preclinical efficacy" standard an International Society for Heart and Lung Transplantation (ISHLT) committee proposed as a premise for launching clinical trials in cardiac xenotransplantation.…”

“…The results "fulfill for the first time the preclinical efficacy" standard an International Society for Heart and Lung Transplantation (ISHLT) committee proposed as a premise for launching clinical trials in cardiac xenotransplantation. 2,4 Did Reichart et al 2 finally capture the carrot and take, what they call "the final step toward clinical xenotransplantation" or did they just advance the stick, with unenumerated barriers keeping clinical application beyond reach?…”

“…Yet, after repeatedly claiming to have met or exceeded the standard for clinical application of xenotransplantation, 2,3 Reichart et al 2 now demurs, saying only that "more experiments will be necessary." But, the justification for more experiments is unpersuasive.…”

“…We suspect porcine cardiac xenografts in non-human primates might overestimate or misrepresent the barriers to clinical xenotransplantation. 8 The xenografts reported by Mohiuddin et al 6 and Reichart et al 2 were from pigs engineered to express human CD46 and human thrombomodulin to better regulate complement and coagulation in recipients. Yet, these and other proteins interact inefficiently with cognate partners in baboons.…”