title: Magnetic resonance tracking of endothelial progenitor cells labeled with alkyl-polyethylenimine 2 kDa/superparamagnetic iron oxide in a mouse lung carcinoma xenograft model.
abstract: The potential of using endothelial progenitor cells (EPCs) in novel anticancer therapy and the repair of vascular injury has been increasingly recognized. In the present study, EPCs were labeled with N-alkyl-polyethylenimine 2 kDa (PEI2k)-stabilized superparamagnetic iron oxide (SPIO) to facilitate magnetic resonance imaging (MRI) of EPCs in a mouse lung carcinoma xenograft model. EPCs derived from human peripheral blood were labeled with alkyl-PEI2k/SPIO. The viability and activity of labeled cells were evaluated using proliferation, migration, and tubulogenesis assays. Alkyl-PEI2k/SPIO-labeled EPCs were injected intravenously (group 1) or mixed and injected together with A549 cells subcutaneously (group 2) into groups of six mice with severe combined immunodeficiency. The labeling efficiency with alkyl-PEI2k/SPIO at 7 μg Fe/mL concentration was approximately 100%. Quantitative analysis of cellular iron was 6.062 ± 0.050 pg/cell. No significant effects on EPC proliferation, migration, or tubulogenesis were seen after labeling. Seven-tesla micro-MRI showed the presence of schistic or linear hypointense regions at the tumor margins starting from days 7 to 8 after EPC administration. This gradually extended into the inner tumor layers in group 1. In group 2, tumor growth was accompanied by dispersion of low-signal intensity regions inside the tumor. Iron-positive cells identified by Prussian blue dye were seen at the sites identified using MRI. Human CD31-positive cells and mouse CD31-positive cells were present in both groups. Labeling EPCs with alkyl-PEI2k/SPIO allows noninvasive magnetic resonance investigation of EPC involvement in tumor neovasculature and is associated with excellent biocompatibility and MRI sensitivity.
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Xia
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Ai
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Liu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Xu
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Xiao
authors.forename: Fabao
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics*; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000637:transplantation; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011094:Polyethyleneimine / Q000737:chemistry / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles; D011094:Polyethyleneimine