PURPOSE: Combining specific and quantitative F-19 magnetic resonance imaging (MRI) with sensitive and convenient optical imaging provides complementary information about the distribution and viability of transplanted pancreatic islet grafts. In this study, pancreatic islets (PIs) were labeled with positively charged multimodal nanoparticles based on poly(lactic-co-glycolic acid) (PLGA-NPs) with encapsulated perfluoro-15-crown-5-ether and the near-infrared fluorescent dye indocyanine green. PROCEDURES: One thousand and three thousand bioluminescent PIs were transplanted into subcutaneous artificial scaffolds, which served as an alternative transplant site. The grafts were monitored using in vivo F-19 MR, fluorescence, and bioluminescence imaging in healthy rats for 2 weeks. RESULTS: Transplanted PIs were unambiguously localized in the scaffolds by F-19 MRI throughout the whole experiment. Fluorescence was detected in the first 4 days after transplantation only. Importantly, in vivo bioluminescence correlated with the F-19 MRI signal. CONCLUSIONS: We developed a trimodal imaging platform for in vivo examination of transplanted PIs. Fluorescence imaging revealed instability of the fluorescent dye and its limited applicability for longitudinal in vivo studies. A correlation between the bioluminescence signal and the F-19 MRI signal indicated the fast clearance of PLGA-NPs from the transplantation site after cell death, which addresses a major issue with intracellular imaging labels. Therefore, the proposed PLGA-NP platform is reliable for reflecting the status of transplanted PIs in vivo.

• Keywords
• F-19 magnetic resonance imaging, Nanoparticles, Optical imaging, Pancreatic islets, Transplantation,
• MeSH
• Endocytosis MeSH
• Fluorine chemistry   MeSH
• Fluorescence MeSH
• Islets of Langerhans diagnostic imaging   MeSH
• Luminescent Measurements * MeSH
• Magnetic Resonance Imaging * MeSH
• Models, Animal MeSH
• Molecular Imaging * MeSH
• Rats, Inbred Lew MeSH
• Rats, Transgenic MeSH
• Tissue Survival MeSH
• Tissue Scaffolds chemistry   MeSH
• Islets of Langerhans Transplantation * MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Fluorine MeSH

Manganese-zinc ferrite nanoparticles were synthesized by using a hydrothermal treatment, coated with silica, and then tested as efficient cellular labels for cell tracking, using magnetic resonance imaging (MRI) in vivo. A toxicity study was performed on rat mesenchymal stem cells and C6 glioblastoma cells. Adverse effects on viability and cell proliferation were observed at the highest concentration (0.55 mM) only; cell viability was not compromised at lower concentrations. Nanoparticle internalization was confirmed by transmission electron microscopy. The particles were found in membranous vesicles inside the cytoplasm. Although the metal content (0.42 pg Fe/cell) was lower compared to commercially available iron oxide nanoparticles, labeled cells reached a comparable relaxation rate R 2, owing to higher nanoparticle relaxivity. Cells from transgenic luciferase-positive rats were used for in vivo experiments. Labeled cells were transplanted into the muscles of non-bioluminescent rats and visualized by MRI. The cells produced a distinct hypointense signal in T2- or T2*-weighted MR images in vivo. Cell viability in vivo was verified by bioluminescence.

• Keywords
• cell labeling, cell transplantation, doping, magnetic resonance imaging, nanoparticles,
• Publication type
• Journal Article MeSH

Subcutaneously implanted polymeric scaffolds represent an alternative transplantation site for pancreatic islets (PIs) with the option of vascularisation enhancement by mesenchymal stem cells (MSC). Nevertheless, a proper timing of the transplantation steps is crucial. In this study, scaffolds supplemented with plastic rods were implanted into diabetic rats and two timing schemes for subsequent transplantation of bioluminescent PIs (4 or 7 days after rod removal) were examined by multimodal imaging. The cavities were left to heal spontaneously or with 10 million injected MSCs. Morphological and vascularisation changes were examined by MRI, while the localisation and viability of transplanted islets were monitored by bioluminescence imaging. The results show that PIs transplanted 4 days after rod removal showed the higher optical signal and vascularisation compared to transplantation after 7 days. MSCs slightly improved vascularisation of the graft but hindered therapeutic efficiency of PIs. Long-term glycaemia normalisation (4 months) was attained in 80% of animals. In summary, multimodal imaging confirmed the long-term survival and function of transplanted PIs in the devices. The best outcome was reached with PIs transplanted on day 4 after rod removal and therefore the suggested protocol holds a potential for further applications.

• MeSH
• Allografts MeSH
• Diabetes Mellitus, Experimental * diagnostic imaging   surgery   MeSH
• Rats MeSH
• Islets of Langerhans * blood supply   diagnostic imaging   metabolism   pathology   MeSH
• Luminescent Measurements * MeSH
• Mesenchymal Stem Cells metabolism   pathology   MeSH
• Rats, Transgenic MeSH
• Graft Survival * MeSH
• Tissue Scaffolds * MeSH
• Islets of Langerhans Transplantation methods   MeSH
• Mesenchymal Stem Cell Transplantation MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

PURPOSE: An artificial site for cell or pancreatic islet transplantation can be created using a polymeric scaffold, even though it suffers subcutaneously from improper vascularisation. A sufficient blood supply is crucial for graft survival and function and can be enhanced by transplantation of mesenchymal stem cells (MSCs). The purpose of this study was to assess the effect of syngeneic MSCs on neoangiogenesis and cell engraftment in an artificial site by multimodal imaging. PROCEDURES: MSCs expressing a gene for luciferase were injected into the artificial subcutaneous site 7 days after scaffold implantation. MRI experiments (anatomical and dynamic contrast-enhanced images) were performed on a 4.7-T scanner using gradient echo sequences. Bioluminescent images were acquired on an IVIS Lumina optical imager. Longitudinal examination was performed for 2 months, and one animal was monitored for 16 months. RESULTS: We confirmed the long-term presence (lasting more than 16 months) of viable donor cells inside the scaffolds using bioluminescence imaging with an optical signal peak appearing on day 3 after MSC implantation. When compared to controls, the tissue perfusion and vessel permeability in the scaffolds were significantly improved at the site with MSCs with a maximal peak on day 9 after MSC transplantation. CONCLUSIONS: Our data suggest that the maximal signal obtained by bioluminescence and magnetic resonance imaging from an artificially created site between 3 and 9 days after MSC transplantation can predict the optimal time range for subsequent cellular or tissue transplantation, including pancreatic islets.

• Keywords
• Bioluminescence, DCE, Dynamic contrast-enhanced MRI, Magnetic resonance imaging, Mesenchymal stem cells, Vascularisation,
• MeSH
• Contrast Media MeSH
• Luminescent Measurements MeSH
• Magnetic Resonance Imaging MeSH
• Mesenchymal Stem Cells cytology   MeSH
• Multimodal Imaging * MeSH
• Rats, Inbred Lew MeSH
• Regional Blood Flow physiology   MeSH
• Reproducibility of Results MeSH
• Tissue Scaffolds MeSH
• Mesenchymal Stem Cell Transplantation * MeSH
• Artificial Cells * MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Contrast Media MeSH

INTRODUCTION: Magnetic nanoparticles (NPs) represent a tool for use in magnetic resonance imaging (MRI)-guided thermoablation of tumors using an external high-frequency (HF) magnetic field. To avoid local overheating, perovskite NPs with a lower Curie temperature (T c) were proposed for use in thermotherapy. However, deposited power decreases when approaching the Curie temperature and consequently may not be sufficient for effective ablation. The goal of the study was to test this hypothesis. METHODS: Perovskite NPs (T c =66°C-74°C) were characterized and tested both in vitro and in vivo. In vitro, the cells suspended with NPs were exposed to a HF magnetic field together with control samples. In vivo, a NP suspension was injected into a induced tumor in rats. Distribution was checked by MRI and the rats were exposed to a HF field together with control animals. Apoptosis in the tissue was evaluated. RESULTS AND DISCUSSION: In vitro, the high concentration of suspended NPs caused an increase of the temperature in the cell sample, leading to cell death. In vivo, MRI confirmed distribution of the NPs in the tumor. The temperature in the tumor with injected NPs did not increase substantially in comparison with animals without particles during HF exposure. We proved that the deposited power from the NPs is too small and that thermoregulation of the animal is sufficient to conduct the heat away. Histology did not detect substantially higher apoptosis in NP-treated animals after ablation. CONCLUSION: Magnetic particles with low T c can be tracked in vivo by MRI and heated by a HF field. The particles are capable of inducing cell apoptosis in suspensions in vitro at high concentrations only. However, their effect in the case of extracellular deposition in vivo is questionable due to low deposited power and active thermoregulation of the tissue.

• Keywords
• MRI, high-frequency magnetic field, hyperthermia, perovskite nanoparticles, tumor ablation,
• MeSH
• Ablation Techniques instrumentation   methods   MeSH
• Hyperthermia, Induced methods   MeSH
• Contrast Media * chemistry   pharmacokinetics   MeSH
• Magnetic Resonance Imaging instrumentation   methods   MeSH
• Magnets MeSH
• Cell Line, Tumor MeSH
• Nanoparticles * chemistry   MeSH
• Silicon Dioxide chemistry   MeSH
• Oxides chemistry   MeSH
• Rats, Wistar MeSH
• Calcium Compounds chemistry   MeSH
• Suspensions MeSH
• Temperature MeSH
• Titanium chemistry   MeSH
• Xenograft Model Antitumor Assays MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Contrast Media * MeSH
• Silicon Dioxide MeSH
• Oxides MeSH
• perovskite MeSH Browser
• Calcium Compounds MeSH
• Suspensions MeSH
• Titanium MeSH