Future perspectives

Future perspectives

Contemporary immunosuppressive therapies and modern surgical and perioperative techniques have all contributed to improved outcomes. The principal innovations being investi gated for the future are aimed at increasing donor availability and improving the long-term survival. Xenotransplantation has been extensively investigated with the use of transgenic pig hearts. In 1964, Hardy perfor a xenotransplant using a chimpanzee heart that beat for 90 minutes before failing, and in 1984 infant Ste phanie Fae Beau clair (often referred to as Baby Fae) famously lived for 21 days after receiving a baboon heart. Gene-editing techniques that allow modification of antigen expression are among the big gest technological breakthroughs to support the resurgence of xenotransplanta tion. Knockout pigs that lack swine leukocyte antigens to reduce organ immunogenicity ha ve led to pig to-primate allograft survival of up to 945 days. Despite the technical and scientific challenges the first contemporary pig- to-human transplant was undertaken in 2022 at the University of Maryland, USA, with good early clinical xenograft func tion using a pig heart with 10 genetic modifications, including four knockouts (thr ee responsible for rapid antibody-mediated rejection of pig organ and one to prevent excessiv e growth) and six human genes added to increase the likelihood of accep tance. Rejection in the medium and long term and the hazard of infection transmission with porcine retroviruses remain of concern. The problems faced by xenotransplantation could be overcome b y organ engineering. Decellularised extracellular matrix sca ff olds of hearts can be created by removing cellular tissue then re populating with autologous cardiac cells. Auto matic contractility has been demonstrated. In addition to finding new sources of donor organs, improve ment of long-term survival remains a priority . New agents to - more favourable side-e ff ect profile remain under investigation. The induction of tolerance of the recipient immune system to donor antigens has promise and T -cell co-stimulation block - ade, mixed chimerism (recipient bone marrow engraftment with donor bone marrow cells) and regulatory T-cell infusions are being studied. Personalisation of current immunosuppres - sants to individual patients may allow for adjustments based on molecular diagnostic techniques to increase e ffi cacy and - reduce side e ff ects. Future perspectives

Bioengineered artificial lung technology using recipient cells grown onto a decellularised lung sca ff old is under development and will avoid an immune response; however, it remains a long way from clinical reality . Success would permit lung transplan tation without the need for immunosuppression, waiting lists or rejection. Artificial lungs, mimicking the success of V ADs in heart transplantation, remain elusive. The physical volume of mem brane oxygenators is too great f or implantation within the thorax and devices are not durable, lasting weeks rather than months or years . Membranes are thrombogenic and high levels of anticoagulation would be required.