Tri-modal In vivo Imaging of Pancreatic Islets Transplanted Subcutaneously in Mice

Abstract

Purpose

Transplantation of pancreatic islets (PIs) is a promising therapeutic approach for type 1 diabetes. The main obstacle for this strategy is that the outcome of islet engraftment depends on the engraftment site. It was our aim to develop a strategy for using non-invasive imaging techniques to assess the location and fate of transplanted PIs longitudinally in vivo.

Procedures

In order to overcome the limitations of individual imaging techniques and cross-validate findings by different modalities, we have combined fluorine magnetic resonance imaging (F-19 MRI), fluorescence imaging (FLI), and bioluminescent imaging (BLI) for studying subcutaneously transplanted PIs and beta cell-like cells (INS-1E cell line) in vivo. We optimized the transduction (using lentiviral vectors) and labeling procedures (using perfluoro crown ether nanoparticles with a fluorescence dye) for PIs and INS-1E cell imaging.

Results

The feasibility of using the proposed imaging methods for PI assessment was demonstrated both in vitro and in vivo. Our data suggested that F-19 MRI is suitable for high-resolution localization of transplanted cells and PIs; FLI is essential for confirmation of contrast localization by histology; and BLI is a reliable method to assess cell viability and survival after transplantation. No significant side effects on cell viability and function have been observed.

Conclusions

The proposed tri-modal imaging platform is a valuable approach for the assessment of engrafted PIs in vivo. It is potentially suitable for comparing different transplantation sites and evaluating novel strategies for improving PI transplantation technique in the future.

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Acknowledgments

We thank Mrs. Tinne Buelens, Mrs. Amy Hillen, and Mrs. Ann Van Santvoort for technical support.

Funding

This work was supported by grants from the Flemish Government FWO project G.0A75.14 and G.0B28.14, from the Agency for Innovation by Science and Technology (IWT 130065 (SBO MIRIAD) and IWT 140061 (SBO NanoCoMIT)), from the European Commission (FP7-MC-ITN Betatrain (289932) and FP7-NMP VIBRANT (228933)), and from the KU Leuven program financing IMIR (PF 2010/017).

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Correspondence to Uwe Himmelreich.

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Liang, S., Louchami, K., Holvoet, B. et al. Tri-modal In vivo Imaging of Pancreatic Islets Transplanted Subcutaneously in Mice. Mol Imaging Biol 20, 940–951 (2018). https://doi.org/10.1007/s11307-018-1192-0

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Key words

  • Pancreatic islet
  • Transplantation
  • Subcutaneous
  • Multimodal imaging
  • Fluorine-19 magnetic resonance imaging
  • Fluorescent imaging
  • Bioluminescent imaging