Through clinical observation, we present an assessment of the autologous mesenchymal stem cells effectiveness in treatment of liver cirrhosis of alimentary etiology. In order to determine the localization of the implanted cell structures, the stem cells were previously labeled with iron (II, III) oxide nanoparticles (IONPs). Further MRI visualization helped to detect the cell structures stained with iron oxide nanoparticles in the human body. In 6 months after the cell therapy, the patient underwent clinical and biochemical blood tests, MEGX test, elastography and subjective health assessment test. The tests data analysis revealed the improvement of the values of all examined parameters after the cell treatment. Also in 6 and 12 months after the treatment, a liver biopsy was performed from the area where the implanted stem cells were visualized. In histological examination of liver bioptates obtained from the area of MSC transplantation, the largest number of stained cells was observed in liver micronodes, as well as at the boundaries of micronodes and fibrous septa. A portion of the bioptate obtained in 12 months after transplantation was used to produce primary cell cultures. Before the first re-seeding of the cultures, cell colonies of both fibroblast-like morphology and epithelial were detected in them. Both types of colonies contained the particles. Conducting the cell therapy to a patient with liver cirrhosis of alimentary etiology contributed to improving the laboratory and instrumental examinations indicators. The patient had come through the treatment procedure satisfactorily, no complications were registered.
This study evaluated the feasibility of using uncoated iron (II, III) oxide nanoparticles (IONP) obtained by electric explosion of wire in air for labelling living mesenchymal stromal cells and their subsequent visualization by magnetic resonance imaging (MRI) using 1.5T clinical MRI scanners. The uptake of uncoated IONP by MSC was demonstrated for the wide range of IONP concentration in the cell culture medium. The cells did not change their proliferative activity, viability, and the set of surface markers. IONP obtained by electric explosion of wire in an atmosphere of air had a shape close to spherical. The size of nanoparticles varied from 14 to 136 nm according to dynamic lateral light scattering, laser diffraction, and transmission electron microscopy. Particles up to 136 nm comprised 75%, and particles less than 36 nm --- 10% of the IONP powder. A wide range of particle sizes made it possible to select MRI parameters suitable for labelled cells detection in animal tissues both in the T2 mode and in the T1 relaxation mode.
Rationale. The need to find the most effective ways to restore liver function in cirrhosis. Goal. To evaluate the effectiveness of using cellular technologies in liver cirrhosis in an experiment.Materials and methods. The experiment included 132 individuals of c57black mice aged 12 to 18 weeks. All individuals are divided into 5 groups (30 individuals in group’s №1– №3, №5 and 12 individuals in group №4). Individuals of group 5 were removed from the experiment before it began in order to determine the normal weight of the liver and spleen. A model of liver cirrhosis was created for individuals of groups 1– 4. Group 4 individuals were removed from the experiment 30 days after the model was formed to confirm the presence of liver cirrhosis. Individuals of group 1 were given intravenous stem cells. Individuals of group 2 were intraportally injected with stem cells. Individuals of group 3 were not injected with stem cells. Changes in all three groups were evaluated 30 days after cell therapy.Results. Against the background of cell therapy, the greatest decrease in liver mass is observed in group 2 (intraportal administration of stem cells), where the liver mass exceeds normal values by 7%. In second place is group 1 (intravenous administration of stem cells), where the liver mass is higher than normal by 17%. In group 3, the liver mass exceeds normal values by 25.3%. The spleen mass 30 days after the application of cell technologies in the second group differed from normal values by 0.01 g; in group 1-by 0.06 g; in group 3-by 0.1 g. The level of total protein 30 days after the introduction of stem cells in group 1 increased by 5.9%; in group 2 by 28.8%; in group 3 by 1.1%. Albumin levels increased by 11% in group 1, 33.8% in group 2, and remained unchanged in group 3. The ALT level in group 1 decreased by 32.3%, in group 2 by 48.1%, and in group 3 remained unchanged. The AST level decreased by 7% in group 1, by 25.9% in group 2, and remained unchanged in group 3. Indicators of alkaline phosphatase decreased by 3.9% in group 1, by 14.3% in group 2, and did not improve in group 3.Conclusion. The use of cellular technologies in liver cirrhosis contributes to a faster recovery of liver function when intraportal introduction of cellular structures.
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