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Updated: Jul 15, 2026
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Transplantation of Bioengineered Lung Using Decellularized Mouse Lungs and Primary Human Endothelial Cells
Published on: March 28, 2025
Life-supporting function of genetically modified swine lungs in baboons
Bao-Ngoc H Nguyen1, Agnes M Azimzadeh, Tianshu Zhang
1University of Maryland and Baltimore Veterans Administration Medical Center, Baltimore, USA.
Summary
Galactosyl transferase knockout swine lungs show improved in vivo survival and reduced hyperacute rejection compared to controls. However, dysregulated coagulation and thrombosis still mediate xenograft injury in these modified lungs.
Area of Science:
- Transplantation immunology
- Xenotransplantation research
- Swine and baboon models
Background:
- Galactosyl transferase knockout swine lungs demonstrate prolonged ex vivo survival with human blood.
- Wild-type and human decay accelerating factor-expressing swine lungs have significantly shorter survival times.
- This study investigates the in vivo performance of galactosyl transferase knockout swine lungs.
Purpose of the Study:
- To evaluate the in vivo behavior and efficacy of galactosyl transferase knockout swine lungs as xenografts.
- To compare the performance of galactosyl transferase knockout lungs against baboon allografts and CD46 transgenic swine xenografts.
- To assess physiological responses, complement activation, and coagulation in recipients of swine lung xenografts.
Main Methods:
- Three galactosyl transferase knockout swine left lungs were transplanted into baboons.
- A baboon lung allograft and two human membrane cofactor protein (CD46) transgenic swine lung xenografts served as controls.
- Physiological parameters, complement activation (C3a), C5b-9 deposition, and cellular sequestration were monitored.
Main Results:
- Two of three galactosyl transferase knockout lungs supported life for 90 and 215 minutes with low pulmonary vascular resistance.
- Control membrane cofactor protein lungs failed within 21 minutes due to high pulmonary vascular resistance.
- Galactosyl transferase knockout lungs showed minimal complement activation but exhibited coagulation activation, platelet activation, and thrombosis.
Conclusions:
- Galactosyl transferase knockout swine lungs are protected from hyperacute lung rejection's immediate physiological consequences in vivo.
- Dysregulated coagulation, thrombin generation, platelet activation, and intravascular thrombosis remain key factors causing injury to these xenografts.
- Further strategies are needed to mitigate coagulation-related complications for successful swine-to-baboon lung xenotransplantation.
