C8: Strategies in preclinical cardiac xenotransplantation

Sucessful preclinical, life-supporting xenogeneic heart-transplantation (xHTx) depends on: (1) intrathoracic heterotopic xHTx, or non-ischemic myocardial preservation (NIMP) when using the orthotopic method. NIMP will also be necessary for transfer of xenogeneic organs for clinical use within Europe; (2) clinically acceptable immunosuppression based on either anti-CD40 or (non-thrombogenic) PASylated anti-CD40L Fab; (3) genetic modifications (gm) of donor animals, such as GTKO/hCD40/hTM or GTKO/hCD46,55,59/hTM, plus anti-inflammatory/anti-apoptotic HO-1/A20). The same modifications in minipigs might be help counteract porcine cardiac overgrowth, which is a problem within a narrow baboon`s chest, but not necessary for future human transplants.