title: Detection of viability of transplanted beta cells labeled with a novel contrast agent - polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles by magnetic resonance imaging.
abstract: Islets can be visualized on MRI by labeling with superparamagnetic contrast agent during the transplantation procedure. However, whether the signal intensity reflects the cell number and cellular viability has not been determined. We used a self-synthesized novel superparamagnetic contrast agent -polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) - to label β-TC-6 cells (a mouse insulinoma cell line) or primary islets with commercial Feridex as a control. The labeling efficiency of two agents was compared by Prussian blue staining, intracellular iron content determination and MR scanning. Cells were exposed to hypoxia, high-glucose or exogenous H₂O₂ stimulation before/after PVP-SPIO labeling. Normal and injured cells were also transplanted into renal subcapsule. A clinically used 3.0 T MR scan was performed in vitro and 24 h post-transplantation to investigate the correlation between cellular viability and signal. Our PVP-SPIO displayed superior biocompatibility and magnetic properties. All of the cells could be labeled at 100 µg/ml iron concentration after 24 h incubation. At 100 µg/ml iron concentration, 1 × 10⁵ β cells labeled with PVP-SPIO could already be visualized in vitro by MRI, less than the detection threshold of Feridex. There existed a linear correlation between the number of labeled cells and R₂ value on the T₂ -weighted images. The signal intensity and the intracellular iron content declined along with the decreased viability of labeled cells. There was also a significant difference in signal intensity between injured and normal labeled cells after transplantation. From these results, we concluded that PVP-SPIO possessed superior cell labeling efficiency, and β cells could be labeled without compromising viability and function. The signal intensity on MRI might be a useful predictor to evaluate the number and the viability of PVP-SPIO-labeled cells.
authors.affiliation: Department of Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Biao
authors.initials: B
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Xie
authors.forename: Muxing
authors.initials: M
authors.lastname: Kang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Chuanxin
authors.initials: C
authors.lastname: Zhai
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media / Q000032:analysis* / Q000493:pharmacokinetics; D003911:Dextrans / Q000032:analysis / Q000493:pharmacokinetics; D005295:Ferrocyanides; D005947:Glucose / Q000494:pharmacology; D006085:Graft Survival; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007340:Insulinoma / Q000473:pathology; D058085:Iron Compounds / Q000032:analysis* / Q000493:pharmacokinetics; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D010087:Oxides / Q000032:analysis* / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000473:pathology; D011205:Povidone / Q000031:analogs & derivatives / Q000032:analysis* / Q000493:pharmacokinetics; D013194:Staining and Labeling; D013370:Subrenal Capsule Assay
chemical_list: D003287:Contrast Media; D003911:Dextrans; D005295:Ferrocyanides; D058085:Iron Compounds; D058185:Magnetite Nanoparticles; D010087:Oxides; C077842:polyvinylpolypyrrolidone; D006861:Hydrogen Peroxide; D011205:Povidone; C065507:ferumoxides; D005947:Glucose; C000170:ferric ferrocyanide