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.

• Klíčová slova
• IBMIR, MRI, Pancreatic islet transplantation, instant blood-mediated inflammatory reaction, liver ischemia, magnetic resonance imaging,
• MeSH
• embolie * komplikace   diagnóza   MeSH
• ischemie * diagnostické zobrazování   etiologie   MeSH
• játra * krevní zásobení   diagnostické zobrazování   patologie   MeSH
• krysa rodu Rattus MeSH
• magnetická rezonanční angiografie metody   MeSH
• přežívání štěpu MeSH
• reprodukovatelnost výsledků MeSH
• teoretické modely MeSH
• transplantace Langerhansových ostrůvků škodlivé účinky   MeSH
• vena portae * MeSH
• vylepšení obrazu metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Magnetoliposomes (MLs) were synthesized and tested for longitudinal monitoring of transplanted pancreatic islets using magnetic resonance imaging (MRI) in rat models. The rat insulinoma cell line INS-1E and isolated pancreatic islets from outbred and inbred rats were used to optimize labeling conditions in vitro. Strong MRI contrast was generated by islets exposed to 50 µg Fe/ml for 24 hours without any increased cell death, loss of function or other signs of toxicity. In vivo experiments showed that pancreatic islets (50-1000 units) labeled with MLs were detectable for up to 6 weeks post-transplantation in the kidney subcapsular space. Islets were also monitored for two weeks following transplantation through the portal vein of the liver. Hereby, islets labeled with MLs and transplanted under the left kidney capsule were able to correct hyperglycemia and had stable MRI signals until nephrectomy. Interestingly, in vivo MRI of streptozotocin induced diabetic rats transplanted with allogeneic islets demonstrated loss of MRI contrast between 7-16 days, indicative of loss of islet structure. MLs used in this study were not only beneficial for monitoring the location of transplanted islets in vivo with high sensitivity but also reported on islet integrity and hereby indirectly on islet function and rejection.

• MeSH
• experimentální diabetes mellitus chemicky indukované   metabolismus   patologie   MeSH
• hyperglykemie metabolismus   patologie   MeSH
• inzulin metabolismus   MeSH
• játra metabolismus   patologie   MeSH
• kontrastní látky metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• Langerhansovy ostrůvky metabolismus   patologie   MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie metody   MeSH
• magnetické nanočástice aplikace a dávkování   MeSH
• potkani inbrední LEW MeSH
• potkani Wistar MeSH
• streptozocin farmakologie   MeSH
• transplantace Langerhansových ostrůvků metody   MeSH
• vena portae metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inzulin MeSH
• kontrastní látky MeSH
• magnetické nanočástice MeSH
• streptozocin MeSH