How mitochondria may point the way toward more successful lung transplants 

A collaboration between researchers at the Mitochondrial Innovation Initiative (MITO2i), Medicine by Design, and University Health Network suggests that changing the temperature at which donated lungs are stored can help maintain mitochondrial health and lead to more successful transplants. 

The current standard temperature to store a donated lung is 4 degrees Celsius (°C), but Ana Cristina Andreazza, a professor in U of T’s Departments of Psychiatry and Pharmacology and Toxicology and Scientific Director of MITO2i, says this puts the organ’s mitochondria — the tiny organelles that power every human cell — into a dormant state that could be impairing transplant outcomes. 

“If we think through the lens of mitochondria metabolism, 4°C is not ideal,” says Andreazza. “When you transplant them from 4°C to a 37°C human body, you can imagine the clash that would happen.” 

To find another strategy, Andreazza teamed up with Shaf Keshavjee, a surgeon-in-chief at the Sprott Department of Surgery at the University Health Network (UHN) and professor in the department of surgery at the University of Toronto. Keshavjee has done extensive work on ex vivo lung perfusion (EVLP), a system that preserves donated lungs outside the body. Dr. Keshavjee’s EVLP work was supported by Medicine by Design; the project title is Lung by Design and the co-investigators include U of T mechanical engineering professors Cristina Amon and Aimy Bazylak, as well as Marcelo Cypel and Tom Wadell, both thoracic surgeons at UHN and professors of surgery at U of T.  

In a paper published in Science Translational Medicine, the team used an animal model to test out a new protocol in which donated lungs were subjected to EVLP at 10°C rather than 4°C. They found that the lungs stored at higher temperatures showed many indications of better function than those stored conventionally at 4°C. As well, their mitochondria had higher levels of molecules that can confer protection against damage. Human patients who received transplants under this protocol had a median time to hospital discharge of 17 days, as compared with 24 days under standard treatment. 

The proof-of-concept study demonstrates the power of multidisciplinary collaboration between mitochondrial experts, clinical surgeons and others to offer new strategies that can directly improve the lives of organ transplant recipients around the world.