Autologous mesenchymal stem cells in treatment of liver cirrhosis: evaluation of effectiveness and visualization method

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

Возможность визуализации распределения в организме человека аутологичных мезенхимальных клеток, введенных в артериальное русло печени

Objective: to visualize the cellular structures entered into the arterial course of a liver, for the purpose of assessment of a possibility of their fixing in liver tissue.Materials and methods. Introduction of mesenchymal stem autologichny cells, marked by iron oxide nanoparticles was carried out to 10 patients with the diagnosis cirrhosis. Introduction was carried out to the arterial course of a liver.Results. The mesenchymal autologichny cages entered into the arterial course of a liver, marked iron oxide nanoparticles, are visualized in tissue of a liver of patients by means of a magnetic and resonant tomography.Conclusion. Mesenchymal autologichny cages, marked iron oxide nanoparticles, it is possible to visualize in a human body by means of a magnetic and resonant tomography. The mesenchymal stem autologichny cells entered into the arterial course of a liver are fixed in liver tissue.Цель исследования: визуализировать вводимые в артериальное русло печени клеточные структуры с целью оценки возможности их фиксации в ткани печени.Материал и методы. Введение мезенхимальных стволовых аутологичных клеток, меченных наночастицами оксида железа, провели 10 пациентам с диагнозом цирроз печени. Введение выполняли в артериальное русло печени.Результаты. Введенные в артериальное русло печени мезенхимальные аутологичные клетки, меченные наночастицами оксида железа, визуализированы в ткани печени пациентов при помощи магнитно-резонансной томографии.Заключение. Мезенхимальные аутологичные клетки, меченные наночастицами оксида железа, возможно визуализировать в организме человека при помощи магнитно-резонансной томографии. Вводимые в артериальное русло печени мезенхимальные стволовые аутологичные клетки фиксируются в ткани печени

Human satellite 3 (HS3) binding protein from the nuclear matrix: isolation and binding properties

AbstractSatellite DNA (satDNA) is the main component of residual DNA in nuclear matrix (NM) preparations. Gel mobility shift assay (GMSA) revealed specific human satellite 3 (HS3) binding activity in NM extracts. An HS3 binding protein was purified using diethylaminoethyl (DEAE)-cellulose and preparative GMSA. The binding was specific, although other satDNA fragments compete to some extent for the binding. DNase I footprinting and methylation interference revealed multiple points of protection distributed throughout the HS3 fragment with periodicity of about 10 bp, mostly inside an AT island. Polyclonal antibodies (AB) were raised against HS3-protein complexes cut from the preparative GMSA gel. On immunoblots, AB recognise a protein, which is not lamin, with apparent molecular mass 70 kDa, the same as revealed by purification (p70). In in situ nuclear matrix preparations combined immunofluorescence (AB) and fluorescent in situ hybridisation (HS3) shows that HS3 and p70 areas correspond to each other. The localisation of this protein detected with AB in interphase nuclei coincides with the heterochromatic regions which surround nucleoli in correspondence with the known HS3 position in the nuclei

Influence of “Chelavite” Mineral Supplement Use on Cadmium and Lead Content in Blood, Wool and Milk of Heavy Cows

The purpose of this research was to study the influence of this supplement use on the concentration of cadmium and lead in blood serum, wool and milk of heavy cows. The cows of milking herd of black-and-white breed, of 3-5 years old were the object of research. Their yearly milk production was 6 thousand litters (control and experimental group, each having 15 heads). The cows have been fed according to the balanced ration for heavy cows. The mineral supplement dose was determined according to the instruction for application for cows of experimental group with feed. The curative dose was 0.6 ml for 10 kg of body mass 1 time a day during 30 days. The samples were taken before giving the mineral supplement “Chelavite” and after the course had finished. The device Unicam AAS-939 was used to determine the cadmium and lead content in blood, wool and milk by way of atomic absorption spectrophotometry. It has been found that the cadmium level reduced by 2.35 times, the lead level reduced by 1,5 times in cows blood, the cadmium level reduced by 1.33 times, the lead level reduced by 4.34 times in cows wool, the cadmium level reduced by 2.2 times, the lead level reduced by 3.7 times in cows milk after giving them mineral supplement “Chelavite”. Thus, the application of chelate compounds in form of “Chelavite” for cows reduces concentration of heavy metals such as cadmium and lead. Then this is one of the ways to improve the milk quality

Evaluation of the Possibility of Fixation of Autologous Mesenchymal Stem Cells 
 in Liver Tissue Introduced into the Portal Vein of the Liver in a Patient Suffering 
 from Cirrhosis

To date, there are quite a large number of reports of the use of stem cells in the treatment of various diseases in humans. However, the authors do not provide credible evidence that the introduced stem cells come directly into the target organ. Without a clear understanding of the location of the introduced stem cells, it is difficult to reliably assess the effect of their use. The article gives its own observation about the possibility of imaging in the human body autologous mesenchymal stem cells introduced through the portal vein of the liver to a patient suffering from cirrhosis. Iron oxide nanoparticles were used as labels. A rather simple question was previously solved: how to create a label of such size that the viability of the stem cell was preserved and it could be visualized in the human body when performing magnetic resonance imaging of abdominal organs. Following in vitro studies, the most appropriate stem cell marking embodiment was chosen to provide both adequate imaging and cell viability. After administration of marked table cells, magnetic resonance imaging of abdominal organs was performed to the patient. The introduced stem cells were visualised only in hepatic tissue. According to clinical and biochemical blood tests - no deviations were detected. There were no complications against the background of this procedure. The patient was discharged for outpatient treatment in satisfactory condition.</jats:p

EFFICIENCY OF USING CELLULAR TECHNOLOGIES IN THE TREATMENT OF PATIENTS WITH DIFFUSE LIVER DISEASES

The increase in the number of patients with diffuse liver diseases, the lack of efficacy from conservative treatments that produce long-lasting and stable outcomes, contribute to the search for alternative treatments. The goal is to assess the effectiveness of using autologous mesenchymal stem cells in treating patients with diffuse liver disease. Materials and methods: the study involved 2 groups of patients of 20 people each. The main group included patients who used autologous mesenchymal stem cells (20-25 million) introduced into the vascular liver channel as therapy. The control group included patients who were treated with L-ornithine-L-aspartate 1 package 3 times a day for 30 days. Benchmarks for evaluation of treatment effectiveness were determined 1, 3 and 6 months after the therapy. Results: in the main group, 3 months after treatment, a normalization of platelet levels was observed, whereas in the control group, platelets did not reach normal values and 6 months after treatment. 1 month after treatment, hepatic enzyme levels were normalized in the main group. The result was maintained 6 months after treatment. In the control group, the level of alanine aminotransferase (ALT), alkaline phosphatase and gamma-glutamyl transpeptidase (GGTP) was above normal throughout the observation; the level of aspartate aminotransferase (AST) normalized to 3 months after treatment and then exceeded normal levels again 6 months from the start of therapy. The functional state of the liver according to the results of the lidocaine test at 6 months after treatment was normalized in 70 % of patients of the main group and in 25 % of patients of the control group. Manifestations of encephalopathy regressed in 65 % of patients in the main group and in 10 % of the control group. After 6 months of treatment, patients with low and reduced level of subjective comfort were absent in the main group, while in the control group such patients were 45 and 35 %, respectively. No complications have been identified against the background of the use of cellular technologies. Findings: the use of cellular technologies is an effective and safe way to treat patients with diffuse liver disease. Continuing research in this direction in the future will help to create algorithms for the use of stem cells in the treatment of patients with diffuse liver diseases.</jats:p

Autologous mesenchymal stem cells in treatment of liver cirrhosis: evaluation of effectiveness and visualization method

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.&#x0D; 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.</jats:p

The effectiveness of autologous mesenchymal stem cells in the treatment of liver cirrhosis and the method of their visualization in the patient’s body

Abstract. The effectiveness of the influence of autologous mesenchymal stem cells on the function of liver tissue in liver cirrhosis of alimentary etiology is considered, as well as the possibility of visualization of the introduced cell structures with subsequent cytological confirmation. To be able to track autologous mesenchymal stem cells introduced in the patients body, they were labeled with iron oxide nanoparticles. Visualization of the introduced cell structures was performed using magnetic resonance imaging and ultrasound examination of the liver. 6 months after the cell therapy, clinical and biochemical blood tests, lidocaine test results, elastography indicators were evaluated, and the dynamics of hepatic encephalopathy was evaluated. The effectiveness of using autologous mesenchymal stem cells was evidenced by the improvement of the above indicators. Also, 6 months after treatment, a liver tissue biopsy was performed from the sites of fixation of previously introduced cell structures. Histological examination revealed the largest number of labeled cells in the liver micro-nodes, as well as at the borders of micro-nodes and fibrous septa. The use of cell therapy in a patient suffering from liver cirrhosis of alimentary etiology helped to improve the indicators of laboratory and instrumental research methods. No complications were detected during the procedure.</jats:p