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Transplantation of Bioengineered Lung Using Decellularized Mouse Lungs and Primary Human Endothelial Cells
Published on: March 28, 2025
Genetics and genomics in human lung transplantation
Stavros Garantziotis1, Scott M Palmer
1Duke University Medical Center, Duke Lung and Heart-Lung Transplant Center, Division of Pulmonary, Allergy and Critical Care Medicine, Durham, NC 27710, USA. garantziotis@niehs.nih.gov
Abstract:
Lung transplantation is the only effective treatment for many advanced lung diseases. However, long-term survival after transplantation remains relatively poor, thus limiting the application of lung transplantation to patients with end-stage disease only. Acute and chronic rejection is the main reason for allograft failure. Attempts to treat or prevent rejection have been stymied by our incomplete understanding of the mechanisms leading to this devastating complication and the lack of representative animal models. A systems-biology approach to lung transplantation with the use of genomics and gene expression profiling has led to new insights into the pathogenesis of rejection, by elucidating the mechanisms of T-cell activation and uncovering the role of B cells and innate immunity. Systems-biology approaches, such as genetics and genomics, may allow minimally invasive diagnosis of rejection and permit individually tailored immunosuppressive regimens. Herein we review the emerging application of genomics and genetics to human lung transplantation and highlight the tremendous potential for these approaches to enhance clinical practice and augment our understanding of basic transplant biology.
Insights
Genomics and systems biology offer new insights into lung transplant rejection mechanisms. These approaches promise improved diagnosis and personalized treatments for lung transplant recipients.
Area of Science:
- Immunology
- Genetics
- Transplantation Biology
Background:
- Lung transplantation is a vital treatment for end-stage lung disease, but long-term survival is limited by graft rejection.
- Acute and chronic rejection remain major obstacles, hindering broader application of lung transplantation.
- Current understanding of rejection mechanisms and effective animal models are insufficient.
Purpose of the Study:
- To review the application of genomics and genetics in lung transplantation.
- To highlight how systems biology approaches can improve understanding of transplant rejection.
- To explore the potential for genomics in clinical practice and basic transplant research.
Main Methods:
- Utilizing a systems-biology approach, including genomics and gene expression profiling.
- Analyzing T-cell activation pathways and the roles of B cells and innate immunity.
- Reviewing emerging genetic and genomic applications in human lung transplantation.
Main Results:
- Systems biology has provided new insights into the pathogenesis of lung transplant rejection.
- Genomics and gene expression profiling have elucidated mechanisms of T-cell activation.
- The involvement of B cells and innate immunity in rejection processes has been uncovered.
Conclusions:
- Genomics and genetics are revolutionizing the study of lung transplantation.
- These approaches offer potential for minimally invasive rejection diagnosis.
- Individually tailored immunosuppressive regimens may become feasible through genetic insights.
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