Improved Labeling of Pancreatic Islets Using Cationic Magnetoliposomes.

Rita Garcia Ribeiro,Ashwini Ketkar-Atre,Ivo Lambrichts,Karim Louchami,Ting Yin,Marcel De Cuyper,Willy Malaisse,Tom Struys,Uwe Himmelreich,Abdullah Sener

doi:10.3390/jpm8010012

Abstract

Pancreatic islets (PIs) transplantation is an alternative approach for the treatment of severe forms of type 1 diabetes (T1D). To monitor the success of transplantation, it is desirable to follow the location of engrafted PIs non-invasively. In vivo magnetic resonance imaging (MRI) of transplanted PIs is a feasible cell tracking method; however, this requires labeling with a suitable contrast agent prior to transplantation. We have tested the feasibility of cationic magnetoliposomes (MLs), compared to commercial contrast agents (Endorem and Resovist), by labeling insulinoma cells and freshly isolated rat PIs. It was possible to incorporate Magnetic Ressonance (MR)-detectable amounts of MLs in a shorter time (4 h) when compared to Endorem and Resovist. MLs did not show negative effects on the PIs’ viability and functional parameters in vitro. Labeled islets were transplanted in the renal sub-capsular region of healthy mice. Hypointense contrast in MR images due to the labeled PIs was detected in vivo upon transplantation, while MR detection of PIs labeled with Endorem and Resovist was only possible after the addition of transfection agents. These findings indicate that MLs are suitable to image PIs, without affecting their function, which is promising for future longitudinal pre-clinical and clinical studies involving the assessment of PI transplantation.

Highlights

Type I diabetes (T1D) is a chronic disease that results from autoimmune destruction of insulin-secreting pancreatic beta cells
INS-1E cells were incubated with a series of different concentrations of all the superparamagnetic iron oxide particles (SPIOs)
Prolonged incubation times for islet labeling, and the that Endorem and Resovist have been withdrawn from the market, have compelled researchers to fact that Endorem and Resovist have been withdrawn from the market, have compelled researchers investigate alternatives for these contrast agents [11,12,14,15,16]

Summary

Introduction

Type I diabetes (T1D) is a chronic disease that results from autoimmune destruction of insulin-secreting pancreatic beta cells. The subsequent lack of the insulin hormone leads to increased blood glucose levels and subsequent morbidity. In severe forms of diabetes, the current treatment of insulin administration is inadequate, and pancreatic islet (PI) transplantation is considered as a promising therapeutic alternative, as 20% of patients were insulin independent five years after.

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