XTransplant will revolutionize the treatment of patients with end-stage heart failure by providing high quality xenogeneic donor organs from IP-protected humanized donor pigs.

Due to evolutionary changes, the genomes of pigs and primates/humans are to some extent different. If transplanted into humans, porcine organs would be rejected within minutes. This phenomenon is called hyperacute rejection.

To mitigate or even abolish this phenomenon, porcine hearts need stable genetic modifications. They are “humanized”: important porcine genes are removed using the “gene scissor” CRISPR/Cas9. In one of the resulting DNA gaps, new genes (this time human versions) are inserted in order to produce the human compatible proteins: one omits rejection, the other pathologic blood clotting.

The transplantation of porcine organs into humans raises several ethical, anthropological and societal issues that have to be taken into account in developing these new therapeutic interventions. First of all: Is it ethically acceptable to use genetically modified animals as a source for donor organs in transplantation medicine? What does it mean anthropologically if patients live with live-saving animal organs? How can we minimize the risks of transmission of infectious diseases from the animals to the human organ recipient? How can we balance the potential benefits and risks for patients who undergo a novel xenotransplantation that has not yet been evaluated thoroughly in a large series of patients?

Assessing and taking into account these ethical implications has been an integral part in developing xenotransplantation from bench to bedside in our collaborative research center. In addition to scientific analyses, our group has organized a citizens’ conference in order to inform public deliberation on xenotransplantation and support political decision-making. In their final statement, the participants arrived at an overall positive evaluation and formulated several requirements for the acceptable use of xenotransplantation www.en.egt.med.uni-muenchen.de.

Rigorous and successful preclinical studies are the basis for a responsible balancing of benefits and risks in the first clinical study of xenogeneic heart transplantation. Furthermore, our group has investigated patients’ information needs when enrolling in a xenotransplantation trial, which will help us to design a thorough patient-centered informed consent process. This will enable potential patients for XTransplant’s first clinical study to balance benefits and risks and make a well-informed decision about their participation.

Taking all together, XTransplant's approach and expertise enables the transplantation of humanized, safe and durable organs in a responsible manner.