Xenotransplantation of the Porcine Lung-From Immunological Barriers to Emerging Experimental Strategies.

Lung transplantation is the only long-lasting life-saving treatment for patients with end-stage pulmonary disease, but the ever-growing shortage of suitable donor organs leads to high mortality rates of the afflicted patients. Xenotransplantation, the transplantation of organs across species, has emerged as a promising alternative. This review summarizes the current knowledge on immunological barriers in lung xenotransplantation, including mechanisms of hyperacute, delayed, and chronic rejection. We highlight potential experimental strategies to overcome the various rejection responses. Xenotransplantation of organs such as hearts and kidneys has recently been advanced to clinical trials. However, lung xenotransplantation remains highly challenging due to its specific vascular sensitivity, extraordinary immunogenicity, and the immediate exposure to the external environment. Thus, translating these advances into durable clinical graft function will require lung-specific genetic and pharmacological strategies that directly address the organ's unique immunological vulnerabilities, especially its susceptibility to complement-mediated vascular injury, microvascular coagulopathy, and pulmonary intravascular macrophage activation.