Pint of Postdoc Speaker Recap - Dr. Jenna DiRito

“Normothermic machine perfusion as a platform for assessment and repair”

Dr. Jenna DiRito

Edited by:

Jennifer Blackburn (assisted by Aileen Fernandez)

Abstract:

Despite a severe organ shortage, thousands of kidneys from higher-risk donors go unused each year. These marginal kidneys have an increased susceptibility to ischemia reperfusion injury and the use of these organs may ultimately result in post-transplant complications like graft loss and recipient death. Normothermic machine perfusion (NMP) has emerged as a platform for ex vivo assessment and repair to increase utilization of higher-risk donor organs without increasing risk to the recipient. This system also allows for the study of the pathophysiology of human kidneys in isolation from the rest of the body. After developing an understanding of how marginal kidneys behave during periods of controlled perfusion, one can then rationally design pre-transplant therapies to be delivered exclusively to the organ on the ex vivo circuit.

For our November 2020 Pint of Postdoc Speaker Series, Jenna DiRito shared about a recent study where using 39 human kidneys, she identified that prolonged cold storage induced accumulation of fibrinogen within tubular epithelium. Additionally, restoration of normoxic conditions—either ex vivo during NMP or in vivo following transplant—triggered intravascular release of fibrinogen correlating with red blood cell aggregation, microvascular plugging, and poor perfusion. The combined delivery of plasminogen and tissue plasminogen activator during NMP lysed the plugs and led to a significant reduction in markers of renal injury, improvement in indicators of renal function, and improved delivery of vascular‐targeted nanoparticles. Her work suggests a new mechanism of cold storage injury in marginal organs and provides a simple treatment with immediate translational potential. With the Tietjen Lab and the Section of Transplantation she is designing a clinical trial based on these findings.