People suffering from severe respiratory disorders 1consider lung transplant2 as their last option in the struggle for life. Despite all this progress, survival rates for lung transplants lag far behind those seen with other organ transplants. Hence, doctors and researchers working in the UVA School of Medicine team are always looking for better ways to improve transplantation and minimize its complications.
Leading the way is Swapnil K. Sonkusare who is part of an outstanding UVA’s Department of Molecular Physiology and Biological Physics teams. Some experts called it “ischemia-reperfusion injury” which they discovered through their research on how cells in the lungs change during transplantations. It starts when organs are deprived oxygen rich blood supply leading to rejection or death after transplantation.
Sonkusare’s team might enhance success rates of lung transplants by aiming at these underlying mechanisms that cause ischemia-reperfusion injuries.3
This discovery will greatly benefit transplant recipients because it corrects “primary graft dysfunction,” which is a cause of death < 30 days following lung transplantation among other ways that this condition affects patients’ lives. Moreover, it plays a role in causing “chronic allograft dysfunction” – accounting for most deaths occurring one year after and beyond transplantation. Paradoxically though, according to the National Institutes of Health (NIH), fifty percent of those receiving such organs develop chronic allograft dysfunction within five years.
Sonkusare’s team plans to minimize ischemia-reperfusion injury which is inevitable to a certain extent during transplantation. In this research, they have described an exact mechanism through which ischemia-reperfusion harms blood vessels causing inflammation and other associated problems. Preventing these issues from developing in mice models by blocking critical stages in the pathway opens up possibilities of future treatment for patients requiring transplants.
Sonkusare thinks that they now have some valuable information regarding the cellular basis of lung ischemia-reperfusion injury.
And now, they are looking to test the efficacy of drug molecules, which can in turn, target these mechanisms in various models of lung injury after transplantation. If this is successful, it can lead to improving the success rate of lung transplants.
These ground-breaking discoveries were published in Science Signaling Journal that is known worldwide. Additionally, Sonkusare and Laubach filed a provisional patent. This research was funded through various grants from NIH namely R01HL157407, R01HL142808, R01HL146914 and R01HL167208.
Significance of the Discovery and Why Lung Transplants Lead to Deaths
Majority of lung transplant rejections and deaths after transplants are caused by a process called ischemia-reperfusion injury.
Hypoxia4 is a condition when tissues receive less oxygen than necessary, an example of which is organ transplantation. This results in what is referred to as primary graft dysfunction; death within 30 days following lung transplantation. But beyond that, it also leads to chronic allograft dysfunctions that arise after a year of receiving new lungs. Every five years, fifty percent of those who receive new lungs will have chronic allograft dysfunction.
They stated that this resulted in immune cell activation and subsequent lung injury.” By blocking key steps in this pathway they were able to stop inflammation and lung damage in lab mice (though further research is needed to explore whether it would be useful for human transplant patients).”
This was published on science signaling; it unraveled new insights about cellular mechanisms involved in lung ischemia-reperfusion injury. They have filed a provisional patent application with respect to targeting processes of lung ischemia-reperfusion injury together with Victor Laubach. The research was funded by National Institutes Of Health through their grants.
Because he discovered what has eluded researchers about the causes of ischemia-reperfusion injuries so far; these newly discovered biological pathways can be targeted for increased clinical outcome through improving success rates during lung transplantation and thus increasing survival rates as well as life qualities among recipients of transplants too.
- Warren, Jamie B., and JoDee M. Anderson. “Newborn respiratory disorders.” Pediatrics in review 31.12 (2010): 487-496. ↩︎
- Burguete, Sergio R., et al. “Lung transplant infection.” Respirology 18.1 (2013): 22-38. ↩︎
- Kalogeris, Theodore, et al. “Cell biology of ischemia/reperfusion injury.” International review of cell and molecular biology 298 (2012): 229-317. ↩︎
- Webster, William S., and Dominique Abela. “The effect of hypoxia in development.” Birth Defects Research Part C: Embryo Today: Reviews 81.3 (2007): 215-228. ↩︎