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Assessment of human islet labeling with clinical grade iron nanoparticles prior to transplantation for graft monitoring by MRI

Lepetit-Coiffe, Matthieu
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Published in Cell Transplantation. 2010, vol. 19, no. 12, p. 1573-1585
Abstract Ex vivo labeling of islets with superparamagnetic iron oxide (SPIO) nanoparticles allows posttransplant MRI imaging of the graft. In the present study, we compare two clinical grade SPIOs (ferucarbotran and ferumoxide) in terms of toxicity, islet cellular uptake, and MRI imaging. Human islets (80-90% purity) were incubated for 24 h with various concentrations of SPIOs (14-280 mug/ml of iron). Static incubations were performed, comparing insulin response to basal (2.8 mM) or high glucose stimulation (16.7 mM), with or without cAMP stimulation. Insulin and Perl's (assessment of iron content) staining were performed. Electronic microscopy analysis was performed. Labeled islets were used for in vitro or in vivo imaging in MRI 1.5T. Liver section after organ removal was performed in the same plane as MRI imaging to get a correlation between histology and radiology. Postlabeling islet viability (80 +/- 10%) and function (in vitro static incubation and in vivo engraftment of human islets in nude mice) were similar in both groups. Iron uptake assessed by electron microscopy showed iron inclusions within the islets with ferucarbotran, but not with ferumoxide. MRI imaging (1.5T) of phantoms and of human islets transplanted in rats, demonstrated a strong signal with ferucarbotran, but only a weak signal with ferumoxide. Signal persisted for >8 weeks in the absence of rejection. An excellent correlation was observed between radiologic images and histology. The hepatic clearance of intraportally injected ferucarbotran was faster than that of ferumoxide, generating less background. A rapid signal decrease was observed in rejecting xenogeneic islets. According to the present data, ferucarbotran is the most appropriate of available clinical grade SPIOs for human islet imaging.
Keywords AnimalsCells, CulturedContrast Media/*metabolismCyclic AMP/pharmacologyDextrans/*metabolismGlucose/pharmacologyHumansInsulin/pharmacologyIron/*metabolismIslets of Langerhans/drug effects/*metabolism/ultrastructureIslets of Langerhans Transplantation/*methodsLiver/cytology/metabolismMagnetic Resonance Imaging/*methodsMagnetite NanoparticlesMaleRatsRats, Inbred Lew
PMID: 20719068
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Research groups Chirurgie viscérale (104)
Chirurgie viscérale (HUG)
Couplage cellulaire et connexines (136)
Imagerie cardiaque fonctionnelle (541)
La transplantation d'îlots de Langerhans (623)
Transplantation et hépatologie (905)
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RIS, Frédéric et al. Assessment of human islet labeling with clinical grade iron nanoparticles prior to transplantation for graft monitoring by MRI. In: Cell Transplantation, 2010, vol. 19, n° 12, p. 1573-1585. doi: 10.3727/096368910X515863 https://archive-ouverte.unige.ch/unige:21252

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Deposited on : 2012-05-23

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