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In vivo imaging of islet transplantation

Abstract

Type 1 diabetes mellitus is characterized by the selective destruction of insulin-producing beta cells, which leads to a deficiency in insulin secretion and, as a result, to hyperglycemia. At present, transplantation of pancreatic islets is an emerging and promising clinical modality, which can render individuals with type 1 diabetes insulin independent without increasing the incidence of hypoglycemic events. To monitor transplantation efficiency and graft survival, reliable noninvasive imaging methods are needed. If such methods were introduced into the clinic, essential information could be obtained repeatedly and noninvasively. Here we report on the in vivo detection of transplanted human pancreatic islets using magnetic resonance imaging (MRI) that allowed noninvasive monitoring of islet grafts in diabetic mice in real time. We anticipate that the information obtained in this study would ultimately result in the ability to detect and monitor islet engraftment in humans, which would greatly aid the clinical management of this disease.

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Figure 1: MN-NIRF labeling of human pancreatic islets.
Figure 2: In vivo MRI of islet transplantation under the kidney capsule.
Figure 3: Optical imaging and fluorescence microscopy of transplanted islets in streptozotocin-induced diabetic mice.
Figure 4: In vivo MRI of intrahepatic transplantation of labeled human islets.

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Acknowledgements

Human pancreatic islets were obtained through The Islet Cell Resource Center, Division of Clinical Research, US National Institutes of Health (NIH). This study was supported in part by NIH grant DK071225 to A.M. The authors would like to acknowledge J. Lock and V. Tchipashvili (Joslin Diabetes Center), J. Moore and Pamela Pantazopoulos (Martinos Center for Biomedical Imaging, MGH) for technical support in animal surgery, and J. Pratt for assistance with imaging islet phantoms. Confocal microscopy was performed at the Confocal Microscopy Core at Massachusetts General Hospital with technical assistance from I.A. Bagayev. Electron microscopy was performed at the W.M. Keck Microscope Facility at the Whitehead Institute (Massachusetts Institute of Technology) with technical assistance from N. Watson.

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Correspondence to Anna Moore.

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Supplementary information

Supplementary Figure 1

Confocal microscopy of frozen islet sections. (PDF 120 kb)

Supplementary Figure 2

Electron microscopy of human pancreatic islets labeled with iron oxides. (PDF 290 kb)

Supplementary Figure 3

Representative T2 map showing significant (P = 0.0003) difference between labeled and unlabeled grafts. (PDF 54 kb)

Supplementary Figure 4

Representative T2 map of NOD-SCID mice 2 weeks after transplantation. (PDF 54 kb)

Supplementary Figure 5

Excised kidneys of NOD-SCID 10 d after transplantation. (PDF 112 kb)

Supplementary Figure 6

Confocal microscopy of frozen kidney sections 188 d after transplantation. (PDF 755 kb)

Supplementary Figure 7

Optical imaging of excised liver with transplanted labeled islets. (PDF 34 kb)

Supplementary Methods (PDF 19 kb)

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Evgenov, N., Medarova, Z., Dai, G. et al. In vivo imaging of islet transplantation. Nat Med 12, 144–148 (2006). https://doi.org/10.1038/nm1316

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  • DOI: https://doi.org/10.1038/nm1316

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