Noninvasive Imaging Techniques in Islet Transplantation

Borot, Sophie; Crowe, Lindsey A.; Toso, Christian; Vallée, Jean‐Paul; Berney, Thierry

doi:10.1007/s11892-011-0215-x

Cited by 10 publications

(4 citation statements)

References 55 publications

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“…In human studies, various modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) have been shown to be useful means for quantification of native and transplanted β-cell mass [4]. In contrast to other modalities, bioluminescence imaging (BLI) additionally provides quantifiable data with high throughput and inherently low background; however, it is difficult to use current BLI technology for in situ quantification of human β cells because the light emission quickly diminishes as it propagates through tissues [5]. In experimental animals, an increasing number of studies have proposed successful quantification of β-cell mass using BLI of mice expressing β-cell-specific reporters [6]–[8].…”

Section: Introductionmentioning

confidence: 99%

Bioluminescence Imaging of β Cells and Intrahepatic Insulin Gene Activity under Normal and Pathological Conditions

et al. 2013

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In diabetes research, bioluminescence imaging (BLI) has been applied in studies of β-cell impairment, development, and islet transplantation. To develop a mouse model that enables noninvasive imaging of β cells, we generated a bacterial artificial chromosome (BAC) transgenic mouse in which a mouse 200-kbp genomic fragment comprising the insulin I gene drives luciferase expression (Ins1-luc BAC transgenic mouse). BLI of mice was performed using the IVIS Spectrum system after intraperitoneal injection of luciferin, and the bioluminescence signal from the pancreatic region analyzed. When compared with MIP-Luc-VU mice [FVB/N-Tg(Ins1-luc)VUPwrs/J] expressing luciferase under the control of the 9.2-kbp mouse insulin I promoter (MIP), the bioluminescence emission from Ins1-luc BAC transgenic mice was enhanced approximately 4-fold. Streptozotocin-treated Ins1-luc BAC transgenic mice developed severe diabetes concomitant with a sharp decline in the BLI signal intensity in the pancreas. Conversely, mice fed a high-fat diet for 8 weeks showed an increase in the signal, reflecting a decrease or increase in the β-cell mass. Although the bioluminescence intensity of the islets correlated well with the number of isolated islets in vitro, the intensity obtained from a living mouse in vivo did not necessarily reflect an absolute quantification of the β-cell mass under pathological conditions. On the other hand, adenovirus-mediated gene transduction of β-cell-related transcription factors in Ins1-luc BAC transgenic mice generated luminescence from the hepatic region for more than 1 week. These results demonstrate that BLI in Ins1-luc BAC transgenic mice provides a noninvasive method of imaging islet β cells and extrapancreatic activity of the insulin gene in the liver under normal and pathological conditions.

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Section: Introductionmentioning

confidence: 99%

Bioluminescence Imaging of β Cells and Intrahepatic Insulin Gene Activity under Normal and Pathological Conditions

et al. 2013

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“…[ 32 ]. Since a major limitation of bioluminescence imaging is that the transmission of signals can be significantly attenuated by tissue absorption and scattering, limiting the ability to detect signals from deep within the body, bioluminescence imaging can only be applied in small animal models [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

In Vivo Imaging of Immune Rejection of MIN6 Cells Transplanted in C3H Mice

Juang,

Chen,

Kao

et al. 2024

Cells

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Recently, we successfully utilized noninvasive magnetic resonance and bioluminescence imaging to track MIN6 cells subcutaneously transplanted in immunocompromised nude mice for up to 64 days. In this study, we further used bioluminescence imaging to investigate the immune rejection of MIN6 cells in immunocompetent C3H mice. A total of 5 × 106 luciferase-transfected MIN6 cells were implanted into the subcutaneous space of each nude or C3H mouse. After transplantation, hypoglycemia and persistent bioluminescence signals were observed in eight of eight (100%) nude mice and five of nine (56%) C3H mice (p < 0.05). We then presensitized a group of C3H mice with C57BL/6 spleen cells just prior to transplantation (n = 14). Interestingly, none of them had hypoglycemia or persistent bioluminescence signals (p < 0.01 vs. C3H mice without presensitization). Histological examination of the grafts revealed a lack or minimal presence of insulin-positive cells in recipients without hypoglycemia and persistent bioluminescence signals. In contrast, recipients with hypoglycemia and persistent bioluminescence signals showed a significant presence of insulin-positive cells in their grafts. Our results indicate that rejection of MIN6 cells occurred in C3H mice and could be enhanced by presensitization with C57BL/6 spleen cells and that bioluminescence imaging is a useful noninvasive tool for detecting rejection of subcutaneously transplanted MIN6 cells.

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“…MRI is possibly the best noninvasive imaging technique to track implanted islets. − This high-resolution whole-body imaging modality allows very good soft tissue contrast. Contrary to computed X-ray tomography, MRI does not use ionizing radiation.…”

Section: Discussionmentioning

confidence: 99%

Magnetic Resonance Imaging of Alginate Beads Containing Pancreatic Beta Cells and Paramagnetic Nanoparticles

Sarkis

Silencieux

Markwick

et al. 2017

ACS Biomater. Sci. Eng.

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Microencapsulation is being investigated as a means to avoid rejection of transplanted pancreatic islets. Monitoring bead distribution and stability in vivo is an important step toward improving microencapsulated islet transplantation strategies. Islet co-encapsulation with gadolinium-labeled mesoporous silica nanoparticles (Gd-MSNs) could allow bead visualization while immobilizing and limiting the potential internalization of the contrast agent. The porous nature of the MSNs could also be used to locally release anti-inflammatory, angiogenic, or anti-apoptotic factors. Mouse insulinoma 6 (MIN6) beta cells were co-encapsulated with Gd-MSNs in alginate beads produced by emulsification and internal gelation. Gd-MSN alginate beads appeared brighter in T 1-weighted imaging sequences (detection threshold of 0.016 mM Gd; relaxometric ratio r 2/r 1 = 1.45) than beads without Gd-MSNs. No leaching of Gd3+ from the hydrogels was detected over the course of 3 months. MIN6 cells co-encapsulated with Gd-MSNs were viable without significant differences in cell growth rate compared to encapsulated controls without Gd-MSNs. This study paves the way for microencapsulated islet tracking via MRI using co-encapsulated paramagnetic nanomaterials.

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Noninvasive Imaging Techniques in Islet Transplantation

Cited by 10 publications

References 55 publications

Bioluminescence Imaging of β Cells and Intrahepatic Insulin Gene Activity under Normal and Pathological Conditions

Bioluminescence Imaging of β Cells and Intrahepatic Insulin Gene Activity under Normal and Pathological Conditions

In Vivo Imaging of Immune Rejection of MIN6 Cells Transplanted in C3H Mice

Magnetic Resonance Imaging of Alginate Beads Containing Pancreatic Beta Cells and Paramagnetic Nanoparticles

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