Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Technical Report
  • Published:

In vivo imaging of islet transplantation

Nature Medicine volume 12, pages 144–148 (2006)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Shapiro, A. et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N. Engl. J. Med. 343, 230–238 (2000).

    Article  CAS  Google Scholar 

  2. Shapiro, A., Ricordi, C. & Hering, B. Edmonton's islet success has indeed been replicated elsewhere. Lancet 362, 1242 (2003).

    Article  Google Scholar 

  3. Moore, A., Bonner-Weir, S. & Weissleder, R. Non-invasive in vivo measurement of beta-cell mass in mouse model of diabetes. Diabetes 50, 2231–2236 (2001).

    Article  CAS  Google Scholar 

  4. Ladriere, L., Leclercq-Meyer, V. & Malaisse, W. Assessment of islet beta-cell mass in isolated rat pancreases perfused with D-[(3)H]mannoheptulose. Am. J. Physiol. Endocrinol. Metab. 281, E298–E303 (2001).

    Article  CAS  Google Scholar 

  5. Malaisse, W. & Ladriere, L. Assessment of B-cell mass in isolated islets exposed to D-[3H]mannoheptulose. Int. J. Mol. Med. 7, 405–406 (2001).

    CAS  PubMed  Google Scholar 

  6. Schmitz, A. et al. Synthesis and evaluation of fluorine-18 labeled glyburide analogs as beta-cell imaging agents. Nucl. Med. Biol. 31, 483–491 (2004).

    Article  CAS  Google Scholar 

  7. Moore, A. et al. MR imaging of insulitis in autoimmune diabetes. Magn. Reson. Med. 47, 751–758 (2002).

    Article  Google Scholar 

  8. Moore, A., Grimm, J., Han, B. & Santamaria, P. Tracking the recruitment of diabetogenic CD8+ T cells to the pancreas in real time. Diabetes 53, 1459–1466 (2004).

    Article  CAS  Google Scholar 

  9. Lu, Y. et al. Bioluminescent monitoring of islet graft survival after transplantation. Mol. Ther. 9, 428–435 (2004).

    Article  CAS  Google Scholar 

  10. Fowler, M. et al. Assessment of pancreatis islet mass after islet transplantation using in vivo bioluminescence imaging. Transplantation 79, 768–776 (2005).

    Article  Google Scholar 

  11. Massoud, T. & Gambhir, S. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 17, 545–580 (2003).

    Article  CAS  Google Scholar 

  12. Moore, A., Medarova, Z., Potthast, A. & Dai, G. In vivo targeting of underglycosylated MUC-1 tumor antigen using a multi-modal imaging probe. Cancer Res. 64, 1821–1827 (2004).

    Article  CAS  Google Scholar 

  13. Moore, A., Weissleder, R. & Bogdanov, A., Jr. Uptake of dextran-coated monocrystalline iron oxides in tumor cells and macrophages. J. Magn. Reson. Imaging 7, 1140–1145 (1997).

    Article  CAS  Google Scholar 

  14. Bulte, J.W. et al. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat. Biotechnol. 19, 1141–1147 (2001).

    Article  CAS  Google Scholar 

  15. Bulte, J., Duncan, I. & Frank, J. In vivo magnetic resonance tracking of magnetically labeled cells after transplantation. J. Cereb. Blood Flow Metab. 22, 899–907 (2002).

    Article  Google Scholar 

  16. Arbab, A. et al. Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. Blood 104, 1217–1223 (2004).

    Article  CAS  Google Scholar 

  17. Jirak, D. et al. MRI of transplanted pancreatic islets. Magn. Reson. Med. 52, 1228–1233 (2004).

    Article  Google Scholar 

  18. Josephson, L., Tung, C., Moore, A. & Weissleder, R. High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. Bioconjug. Chem. 10, 186–191 (1999).

    Article  CAS  Google Scholar 

  19. Bulte, J. et al. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc. Natl. Acad. Sci. USA 96, 15256–15261 (1999).

    Article  CAS  Google Scholar 

  20. Lewin, M. et al. Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat. Biotechnol. 18, 410–414 (2000).

    Article  CAS  Google Scholar 

  21. Arbab, A. et al. Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. Radiology 229, 838–846 (2003).

    Article  Google Scholar 

  22. Zhan, Y. et al. Activated macrophages require T cells for xenograft rejection under the kidney capsule. Immunol. Cell Biol. 81, 451–458 (2003).

    Article  Google Scholar 

  23. Davalli, A. et al. Vulnerability of islets in the immediate posttransplantation period. Dynamic changes in structure and function. Diabetes 45, 1161–1167 (1996).

    Article  CAS  Google Scholar 

Download references

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.

Author information

Author notes

  1. Natalia V Evgenov and Zdravka Medarova: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, 13th Street, Charlestown, 02129, Massachusetts, USA

    Natalia V Evgenov, Zdravka Medarova, Guangping Dai & Anna Moore

  2. Joslin Diabetes Center, 1 Joslin Place, Harvard Medical School, Boston, 02215, Massachusetts, USA

    Susan Bonner-Weir

Authors
  1. Natalia V Evgenov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zdravka Medarova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guangping Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susan Bonner-Weir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anna Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna Moore.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

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)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing