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Updated: Jun 21, 2025
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Left Lung Orthotopic Transplantation in a Juvenile Porcine Model for ESLP
Published on: February 14, 2022
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Future directions for xenotransplantation in lungs.
Hidetaka Hara1, Hisashi Sahara2, Toyofumi Fengshi Chen-Yoshikawa3
1The Transplantation Institute, the Second Affiliated Hospital of Hainan Medical University, Haikou, China.
Current Opinion in Organ Transplantation
|July 11, 2024
Summary
Advancements in genetically modified pig lungs, including humanized von Willebrand factor and CMAH gene knockout, show promise for lung xenotransplantation. These strategies significantly improve graft survival and reduce immune rejection, paving the way for clinical trials.
Area of Science:
- Biomedical Engineering
- Transplantation Immunology
- Xenotransplantation Research
Background:
- Preclinical xenotransplantation studies, particularly for heart and kidney, have advanced significantly.
- Lung xenotransplantation remains a critical area of research due to organ shortages.
- This review focuses on recent breakthroughs in lung xenotransplantation.
Purpose of the Study:
- To assess recent progress in lung xenotransplantation research.
- To evaluate the potential clinical implications of these advancements.
- To identify key strategies for improving xenograft survival and compatibility.
Main Methods:
- Utilizing humanized von Willebrand factor to reduce platelet sequestration.
- Combining human tissue factor pathway inhibitor and CD47 expression with selectin and integrin inhibition.
- Enhancing expression of human complement regulatory proteins and thrombomodulin.
- Genetically engineering pig lungs, including CMAH gene knockout.
- Implementing comprehensive treatment strategies in in-vivo models.
Main Results:
- Humanized von Willebrand factor demonstrated efficacy in reducing platelet sequestration.
- Combined genetic modifications and inhibitors delayed neutrophil and platelet sequestration.
- Engineered pig lungs with human proteins improved graft survival by reducing platelet activation and coagulation disruptions.
- CMAH gene knockout decreased antibody-mediated inflammation and erythrocyte sequestration, enhancing compatibility.
- In-vivo experiments achieved xenograft survival up to 31 days with multiple modifications.
Conclusions:
- Key insights for successful xenotransplantation have been uncovered.
- Further research is needed in immunosuppressive therapy and genetically modified pigs.
- These advancements are crucial for the development of clinical trials in lung xenotransplantation.
- The ultimate goal is to improve outcomes for patients with end-stage lung disease.
