A novel model for in vivo quantification of immediate liver perfusion impairment after pancreatic islet transplantation

Abstract

Instant Blood-Mediated Inflammatory Reaction (IBMIR) is a major cause of graft loss during pancreatic islet transplantation, leading to a low efficiency of this treatment method and significantly limiting its broader clinical use. Within the procedure, transplanted islets obstruct intrahepatic portal vein branches and consequently restrict blood supply of downstream lying liver tissue, resulting typically in ischemic necrosis. The extent of ischemic lesions is influenced by mechanical obstruction and inflammation, as well as subsequent recanalization and regeneration capacity of recipient liver tissue. Monitoring of immediate liver perfusion impairment, which is directly related to the intensity of post-transplant inflammation and thrombosis (IBMIR), is essential for improving therapeutic and preventive strategies to improve overall islet graft survival. In this study, we present a new experimental model enabling direct quantification of liver perfusion impairment after pancreatic islet transplantation using ligation of hepatic arteries followed by contrast-enhanced magnetic resonance imaging (MRI). The ligation of hepatic arteries prevents the contrast agent from circumventing the portal vein obstruction and enables to discriminate between well-perfused and non-perfused liver tissue. Here we demonstrate that the extent of liver ischemia reliably reflects the number of transplanted islets. This model represents a useful tool for in vivo monitoring of biological effect of IBMIR-alleviating interventions as well as other experiments related to liver ischemia. This technical paper introduces a novel technique and its first application in experimental animals.

Advances in Pancreatic Islet Transplantation Sites for the Treatment of Diabetes

“…This produce risk of portal vein thrombosis and other vascular complications, such as variceal bleeding, intravascular coagulation, and intraperitoneal hemorrhage. While the risk for complete thrombosis is rare, partial thrombosis can occur more frequently and affect the function of both transplanted islets and liver, leading to partial liver damage and necrosis ( 115 ). Thrombosis also induces an inflammatory response that is detrimental to long term islet survival.…”

Immune-Protective Formulations and Process Strategies for Improved Survival and Function of Transplanted Islets

“…Portal thrombosis is a life-threatening complication. Portal hypertension might raise the post-transplant bleeding risk, portal thrombosis, and the occurrence of sepsis ( 89 ).…”

Potential Benefits of Nrf2/Keap1 Targeting in Pancreatic Islet Cell Transplantation

“…IBMIR consists of leukocyte infiltration, complement activation, and thrombosis which has been seen on MRI and positron-emission tomography monitoring to lead to a dramatic reduction of islet cells in the very early peri-transplant period [81][82][83][84]. Utilization of Kosinova et al's model for in vivo monitoring of liver ischemia in relation to pancreatic islet cell transplants shows promise as a system capable of quantifying the alleviating extent of inflammation [85] with Nrf2/Keap1 activation.…”