Progress and challenges in lung xenotransplantation: an update

Area of Science:

• Transplantation Biology
• Genetic Engineering
• Immunology

Background:

• Xenotransplantation offers a potential solution to organ shortages.
• Discordant xenotransplantation faces significant immunological barriers.
• Genetic engineering of donor animals is crucial for overcoming these barriers.

Purpose of the Study:

• To review and summarize recent progress in lung xenotransplantation.
• To discuss genetic modifications and interventions for clinical application.
• To address known mechanisms of xeno lung injury.

Main Methods:

• Utilizing transgenic donor pigs with modified complement, coagulation, and inflammatory pathways.
• Employing knockout of major porcine carbohydrates (GalT, Neu5Gc, B4Gal).
• Administering drugs such as thromboxane synthase inhibitors and costimulatory pathway blocking antibodies.

Main Results:

• Transgenic modifications and drug treatments prolonged recipient survival up to 31 days.
• Life-supporting function of lung xenografts was achieved in vivo.
• Inflammation remains the predominant failure mechanism, causing vascular barrier injury.

Conclusions:

• Multitransgenic pigs and targeted drug therapies significantly improve xenograft survival.
• Overcoming delayed vascular barrier injury is essential for clinical relevance.
• Lung xenotransplantation shows promise for clinical application with further research.