Magnetic Resonance Imaging of Pancreatic Islets in Tolerance and Rejection

Kříž, Jan; Jirák, Daniel; Girman, Peter; Berková, Zuzana; Zacharovová, K.; Honsová, Eva; Lodererová, Alena; Hájek, Milan; Saudek, F

doi:10.1097/01.tp.0000183959.73681.b9

Cited by 91 publications

(104 citation statements)

References 20 publications

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“…25,26 These studies reported discrepant results as far as the nature of the cells containing the ferumoxides is concerned: mostly endocrine cells but also some macrophages in the 1 study 25 and exclusively macrophages in the other. 26 However, they both demonstrated rapid loss of the iron-related MR signals after islet rejection. A possible explanation is the difference in the iron-handling properties of the recipient organs, ie, the heart in our study and the liver in the pancreatic islet transplantation studies.…”

Section: Discussionmentioning

confidence: 97%

Magnetic Resonance Imaging Overestimates Ferumoxide-Labeled Stem Cell Survival After Transplantation in the Heart

et al. 2008

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Background-Stem cell labeling with iron oxide (ferumoxide) particles allows labeled cells to be detected by magnetic resonance imaging (MRI) and is commonly used to track stem cell engraftment. However, the validity of MRI for distinguishing surviving ferumoxide-labeled cells from other sources of MRI signal, for example, macrophages containing ferumoxides released from nonsurviving cells, has not been thoroughly investigated. We sought to determine the relationship between the persistence of iron-dependent MRI signals and cell survival 3 weeks after injection of syngeneic or xenogeneic ferumoxides-labeled stem cells (cardiac-derived stem cells) in rats. Methods and Results-We studied nonimmunoprivileged human and rat cardiac-derived stem cells and human mesenchymal stem cells doubly labeled with ferumoxides and ␤-galactosidase and injected intramyocardially into immunocompetent Wistar-Kyoto rats. Animals were imaged at 2 days and 3 weeks after stem cell injection in a clinical 3-T MRI scanner. At 2 days, injection sites of xenogeneic and syngeneic cells (cardiac-derived stem cells and mesenchymal stem cells) were identified by MRI as large intramyocardial signal voids that persisted at 3 weeks (50% to 90% of initial signal). Histology (at 3 weeks) revealed the presence of iron-containing macrophages at the injection site, identified by CD68 staining, but very few or no ␤-galactosidase-positive stem cells in the animals transplanted with syngeneic or xenogeneic cells, respectively. Conclusions-The persistence of significant iron-dependent MRI signal derived from ferumoxide-containing macrophages despite few or no viable stem cells 3 weeks after transplantation indicates that MRI of ferumoxide-labeled cells does not reliably report long-term stem cell engraftment in the heart. (Circulation. 2008;117:1555-1562.)

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Section: Discussionmentioning

confidence: 97%

Magnetic Resonance Imaging Overestimates Ferumoxide-Labeled Stem Cell Survival After Transplantation in the Heart

et al. 2008

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“…One study (40) claimed that SPIO particles were present in lysosomes in ␤-cells of isolated rat islets. However, this claim was subsequently retracted as it appears that their technique was limited to labeling macrophages within the islet (41). Our electron microscope analysis has now clarified the location of SPIO within islet cells.…”

Section: Discussionmentioning

confidence: 98%

Imaging Islets Labeled With Magnetic Nanoparticles at 1.5 Tesla

et al. 2006

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We have developed a magnetic resonance imaging (MRI) technique for imaging Feridex (superparamagnetic iron oxide [SPIO])-labeled islets of Langerhans using a standard clinical 1.5-Tesla (T) scanner and employing steadystate acquisition imaging sequence (3DFIESTA). Both porcine and rat islets were labeled with SPIO by a transfection technique using a combination of poly-L-lysine and electroporation. Electron microscopy demonstrated presence of SPIO particles within the individual islet cells, including ␤-cells and particles trapped between cell membranes. Our labeling method produced a transfection rate of 860 pg to 3.4 ng iron per islet, dependent on the size of the islet. The labeling procedure did not disrupt either the function or viability of the islets. In vitro 3DFIESTA magnetic resonance images of single-labeled islets corresponded with their optical images. In vivo T2*-weighted scan using 1.5 T detected as few as 200 SPIO-labeled islets transplanted under rat kidney capsule, which correlated with immunohistochemistry of the transplant for insulin and iron. Ex vivo 3DFIESTA images of kidneys containing 200, 800 or 2,000 SPIO-labeled islet isografts showed good correlation between signal loss and increasing numbers of islets. These data provide evidence that islets can be labeled with SPIO and imaged using clinically available 1.5-T MRI. Diabetes

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“…and to image them in the livers of diabetic mice using MRI (6)(7)(8)(9). One recent study showed the feasibility of this approach in T1DM patients as well (10) …”

Section: Islet Transplantation Is One Of the Most Promising Therapiesmentioning

confidence: 99%

“…Figure 7E-J), but was not detectable in nonlabeled islets (Figure 7K and L) Comparison between 7.0 T and 1. (6)(7)(8)(9)(10)23 …”

Section: Over Time Iron Uptake By Islets At 28mentioning

confidence: 99%

Improving the Procedure for Detection of Intrahepatic Transplanted Islets by Magnetic Resonance Imaging

Malosio¹,

Esposito

Poletti

et al. 2009

American Journal of Transplantation

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Islet transplantation is an effective therapy for restoring normoglycemia in type-1 diabetes, but long-term islet graft function is achieved only in a minority of cases. Noninvasive magnetic resonance imaging of pancreatic islets is an attractive option for "real-time" monitoring of graft evolution. So far, previous studies have been performed in the absence of a standardized labeling procedure and, besides a feasibility study in patients, the effectiveness and safety of various labeling approaches were tested only with high field magnets (4.7 T). In this study, we addressed: (a) standardization of a labeling procedure for human islets with clinically-approved contrast agent Endorem R , (b) safety aspects of labeling related to inflammation and (c) quality of imaging both at 7 T and 1.5 T. We have highlighted that the ratio of Endorem R /islet is crucial for reproducible labeling, with a ratio of 2.24 ug/IEQ, allowing successful in vivo imaging both with 1.5 T and 7.0 T magnets up to 143 days after intrahepatic transplant. With this standardized labeling procedure, labeled islets are neither inflamed nor more susceptible to inflammatory insults than unlabeled ones. This report represents an important contribution towards the development of a standardized and safe clinical protocol for the noninvasive imaging of transplanted islets in humans.

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Magnetic Resonance Imaging of Pancreatic Islets in Tolerance and Rejection

Abstract: MR imaging of iron-labeled pancreatic islets can be used for verification of the technical success of the transplantation procedure itself and for the detection of the decreasing relative islet mass due to rejection.

Cited by 91 publications

References 20 publications

Magnetic Resonance Imaging Overestimates Ferumoxide-Labeled Stem Cell Survival After Transplantation in the Heart

Magnetic Resonance Imaging Overestimates Ferumoxide-Labeled Stem Cell Survival After Transplantation in the Heart

Imaging Islets Labeled With Magnetic Nanoparticles at 1.5 Tesla

Improving the Procedure for Detection of Intrahepatic Transplanted Islets by Magnetic Resonance Imaging

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