Related Experiment Videos
Lung xenotransplantation.
Hisashi Sahara1, Hironosuke Watanabe, Thomas Pomposelli
1aColumbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA bDivision of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
Current Opinion in Organ Transplantation
|September 6, 2017
Summary
Recent advancements in xeno lung transplantation (XLTx) involve genetically modified pig lungs and novel pharmaceuticals. These strategies improve graft survival, but further innovation is needed for clinical application.
Area of Science:
- Transplantation immunology
- Xenotransplantation research
- Surgical innovation
Background:
- Xeno lung transplantation (XLTx) offers a potential solution to donor organ shortages.
- Early xeno lung graft loss remains a significant barrier to clinical success.
- Understanding rejection mechanisms is crucial for developing effective therapies.
Purpose of the Study:
- To review the latest progress in xeno lung transplantation (XLTx).
- To describe mechanisms of early xeno lung graft loss.
- To outline therapeutic strategies to overcome these challenges.
Main Methods:
- Utilized ex-vivo perfusion models with porcine lungs and human blood.
- Investigated genetically modified pig lungs with novel pharmaceutical interventions.
- Employed in-vivo pig-to-nonhuman primate lung transplant models.
Main Results:
- Genetically modified lungs (GalTKO, N-glycolylneuraminic acid-KO) and complement-regulating genes (hCD46, hCD55) improved survival.
- Modulation of inflammation/coagulation cascades (human leukocyte antigen-E, human thrombomodulin, etc.) showed protective effects.
- Pharmacologic interventions, including macrophage depletion and receptor blockade, extended xenograft survival up to 5 days in primate models.
Conclusions:
- Multitransgenic GalTKO pigs show promise in prolonging xenograft survival.
- Significant limitations persist, hindering clinical translation of XLTx.
- Intensive genetic manipulation and strategies targeting inflammation/coagulation are essential for future XLTx success.