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Study of Fluorescent Magnetic Nanoparticles Labeled Bone Mescenchymal Stem Cells Targeting Gastric Cancer

Author: JiJiaJia
Tutor: CuiDaXiang
School: Shanghai Jiaotong University
Course: Biochemistry and Molecular Biology
Keywords: Bone marrow mesenchymal stem cells Fluorescent magnetic nanoparticles Gastric Cancer Targeted migration
CLC: R329
Type: Master's thesis
Year: 2011
Downloads: 76
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Abstract


Objective: (l) to establish an efficient and simple purification of bone marrow mesenchymal stem cells (bone mesenchymal stem cells, BMSCs) method; (2) clear fluorescent magnetic nanoparticles (fluorescent magnetic nanoparticles, FMNPs) labeled mesenchymal appropriate concentration of stem cells; (3) labeled BMSCs in vitro test FMNPs effect; (4) investigate the migration of BMSCs targeting ability of gastric cancer. Methods: (1) the use of adherent culture isolated and purified rat bone marrow mesenchymal stem cells by flow cytometry of bone marrow mesenchymal stem cells CD29, CD90 and CD45 expression, respectively, with osteoblasts and adipocytes induced agents induce stem cell detection of bone marrow mesenchymal stem cell differentiation capacity; (2) in vitro with different concentrations of FMNPs mark BMSCs, the effects of different concentrations of FMNPs on cell viability, and thus select the best mark FMNPs concentration capacity; using the Prussian blue staining confocal microscopy, magnetic resonance tomography fluorescent magnetic nanoparticles labeled stem cells in vitro imaging results; (3) to establish the model of gastric cancer in nude mice, the application of small animal molecular imaging systems and MRI verification intravenous labeled BMSCs Gastric targeting ability. Results: (1) the use of adherent culture isolated and purified rat bone marrow mesenchymal stem cells by flow cytometry third generation of BMSCs CD29, CD90 and CD45 positive expression rates were 84.69%, 90.28%, 0.72 %, alkaline phosphatase staining and oil red O staining results show that bone marrow mesenchymal stem cells successfully differentiated into osteoblasts and adipocytes; (2) fluorescent magnetic nanoparticles with bone marrow mesenchymal stem cells co-cultured with different time points Stem cell survival, and thus select the best fluorescent labeled magnetic nanoparticles concentration of 50? g / mL. Prussian blue staining and confocal fluorescence imaging and magnetic resonance imaging showed that the success of magnetic nanoparticles in vitro markers of mesenchymal stem cells and does not affect cell viability; (3) to establish nude mice model of gastric cancer, gastric cancer cells injected subcutaneously into nude mice MGC803 , four weeks after the screening of gastric cancer tumorigenicity in nude mice model with good effects and labeled stem cells injected into the tail vein of nude mice after 14 days with a small animal molecular imaging system observed migrating BMSCs site targeted to cancer. Subsequently, the mice were sacrificed, remove the heart, lung, liver, spleen, kidney and tumor blocks from the fluorescence imaging apparatus, the results show the label component of the tumor showed a significant fluorescent signal, in addition to the liver (with the ability to metabolize foreign) , other organs such as the heart, spleen, lung, kidney no fluorescence signal. Another group of FMNPs labeled BMSCs transplantation nude mouse model of gastric cancer after an MRI scan, at the tumor site 3.0 T magnetic field strength under a clear magnetic resonance signals. Conclusions: (l) adherence screening method is simple, easy to filter out cell survival, is a simple and effective method; (2) the appropriate concentration FMNPs efficiently labeled BMSCs; (3) BMSCs with high specificity to target cancer capacity. Significance: This experiment proved BMSCs have targeted the ability to migrate to gastric cancer. In addition, BMSCs have drawn convenient, strong in vitro amplification, gene transfection efficiency is high, stable expression of transfected, autologous transfusion can thus avoiding immune rejection characteristics, genetic engineering is considered ideal seed cells, which is BMSCs as the carrier of gastric cancer in targeted gene therapy provides a theoretical basis. However, at present on BMSCs migration to gastric cancer cell targeting molecular mechanisms are not yet clear, pending further study.

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