Sayuan Liang1,2,3, Karim Louchami1,4, Bryan Holvoet5, Rein Verbeke6, Christophe M Deroose5, Bella Manshian1, Stefaan J Soenen1, Ine Lentacker6, Uwe Himmelreich7. 1. Biomedical MRI, Department of Imaging & Pathology, University of Leuven, Leuven, Belgium. 2. Bio-Imaging Lab, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium. 3. Philips Research China, Shanghai, China. 4. Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Bruxelles, Belgium. 5. Nuclear Medicine & Molecular Imaging, Department of Imaging & Pathology, University of Leuven, Leuven, Belgium. 6. Laboratory for General Biochemistry and Physical Pharmacy, Ghent University, Ghent, Belgium. 7. Biomedical MRI, Department of Imaging & Pathology, University of Leuven, Leuven, Belgium. uwe.himmelreich@med.kuleuven.be.
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.
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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Authors: Shweta Saini; Jennifer Poelmans; Hannelie Korf; James L Dooley; Sayuan Liang; Bella B Manshian; Rein Verbeke; Stefaan J Soenen; Greetje Vande Velde; Ine Lentacker; Katrien Lagrou; Adrian Liston; Conny Gysemans; Stefaan C De Smedt; Uwe Himmelreich Journal: iScience Date: 2019-09-18