Islet transplantation is one of the most promising and effective therapies for restoring normoglycemia in type 1 diabetic (T1D) patients but islet engraftment is one of the main obstacles hampering long-term success. Monitoring graft loss, caused either by immunological or non-immunological events, occurring in the first phase after transplantation and at later stages of patient?s life is a very important issue. Among the imaging approaches previously applied Magnetic Resonance Imaging (MRI) monitoring of islets fate following labeling with superparamagnetic iron oxide agents resulted promising. Aim of this study was to translate into patients the method of islet labeling and MRI monitoring developed in our preclinical setting, and to compare imaging results with graft clinical outcome. Three T1D patients and one non-diabetic patient undergoing auto-transplantation following subtotal pancreasectomy received Endorem?-labeled islets. Patients were monitored by MRI and metabolically (HbA1C, exogenous insulin requirement and C-peptide, TEF) at 1, 3, 7 days following transplantation and once a month up to ten months. Labeled transplanted islets appeared as hypointense areas scattered within the liver parenchyma, whose absolute number at 24hr after transplantation reflected the labeling efficiency. In Pt#1 and 3 with good mid-term graft function, MRI follow-up showed an important early loss of hypointense spots followed by a slow and progressive disappearance at later time points. Graft loss of function in Pt#2 4 weeks after transplantation was associated with the complete disappearance of all hypointense signals. The auto-transplanted patient stably insulin free, showed no significant signal reduction during the first 3 days, followed by loss of spots similar to Pt with good mid-term graft function. These results suggest that MRI monitoring of islet transplantation at early time points could represent a meaningful read-out for helping in predicting transplant failure or success, but its relevance for mid-/long-term islet function assessment appears evanescent.

MR Imaging monitoring of iron labeled pancreatic islets in a small series of patients: islets fate in successful, unsuccessful and auto-transplantation.

Malosio ML corresponding author;
2015

Abstract

Islet transplantation is one of the most promising and effective therapies for restoring normoglycemia in type 1 diabetic (T1D) patients but islet engraftment is one of the main obstacles hampering long-term success. Monitoring graft loss, caused either by immunological or non-immunological events, occurring in the first phase after transplantation and at later stages of patient?s life is a very important issue. Among the imaging approaches previously applied Magnetic Resonance Imaging (MRI) monitoring of islets fate following labeling with superparamagnetic iron oxide agents resulted promising. Aim of this study was to translate into patients the method of islet labeling and MRI monitoring developed in our preclinical setting, and to compare imaging results with graft clinical outcome. Three T1D patients and one non-diabetic patient undergoing auto-transplantation following subtotal pancreasectomy received Endorem?-labeled islets. Patients were monitored by MRI and metabolically (HbA1C, exogenous insulin requirement and C-peptide, TEF) at 1, 3, 7 days following transplantation and once a month up to ten months. Labeled transplanted islets appeared as hypointense areas scattered within the liver parenchyma, whose absolute number at 24hr after transplantation reflected the labeling efficiency. In Pt#1 and 3 with good mid-term graft function, MRI follow-up showed an important early loss of hypointense spots followed by a slow and progressive disappearance at later time points. Graft loss of function in Pt#2 4 weeks after transplantation was associated with the complete disappearance of all hypointense signals. The auto-transplanted patient stably insulin free, showed no significant signal reduction during the first 3 days, followed by loss of spots similar to Pt with good mid-term graft function. These results suggest that MRI monitoring of islet transplantation at early time points could represent a meaningful read-out for helping in predicting transplant failure or success, but its relevance for mid-/long-term islet function assessment appears evanescent.
2015
Istituto di Neuroscienze - IN -
Pancreatic islet transplantation; Type 1 diabetes patients; Autoimmunity; Autologous islet transplantation; Superparamagnetic iron oxide particles (SPIO); Magnetic resonance imaging (MRI); Inflammation; Cytokines
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/281414
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