Before a donor liver is transplanted into an organ recipient, could it be modified to reduce the risk of the recipient’s immune system rejecting the liver? That’s the question Division of Transplantation Assistant Professor David Al-Adra, MD, PhD will begin to explore with a new one-year, $50,000 Pilot Research Award from the American Association for the Study of Liver Diseases Foundation. Al-Adra and his research team are focused on small particles called extracellular vesicles (EVs) that are released by the liver.
According to Al-Adra, “We know that EVs play an important role in determining how the recipient’s immune system responds to a transplanted organ – but we don’t know why certain EVs may help the immune system adjust to the new organ while other EVs may support the immune system’s rejection of a donor organ.”
Al-Adra will be using a liver storage technique called normothermic ex vivo liver perfusion (NEVLP) to study EVs. Rather than placing a donor liver on ice before it is transplanted into the organ recipient, NEVLP allows the transplant team to keep the liver warm by continuously pumping blood through it. This in turn allows the liver to resume its normal physiologic activity while it awaits transplantation.
“NEVLP provides us with a great opportunity to study EVs that are produced directly by the liver,” explained Al-Adra.
The research team plans to pilot test the use of NEVLP to study liver-produced EVs using a rat model of liver transplantation. They will also be testing whether they can modify the environment in which the liver is stored during NEVLP to make the EVs more likely to support regulation of the immune system.
“This study is going to give us a much better understanding of the immune-related function of liver-derived EVs in a transplant setting. We can then use these results to obtain additional research funding so we can gene edit EVs during NEVLP in a way that will help them support regulation of the organ recipient’s immune system, thereby decreasing rejection of the transplanted liver,” said Al-Adra.