scholarly journals Influence of combined transplantation of multipotent mesenchymal stromal cells and stellate liver cells on its morphofunctional state after partial hepatectomy

2021 ◽  
Vol 20 (1) ◽  
pp. 16-22
Author(s):  
I. Yu. Maklakova ◽  
D. Yu. Grebnev ◽  
A. V. Osipenko
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Partial Hepatectomy ◽  
Placental Tissue ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Liver Cells ◽  
Morphometric Parameters ◽  
Laboratory Animals ◽  
Repair System ◽  
Pathological Mitoses

The aim of the study was to study the changes in the morphofunctional state of the liver after the combined transplantation of multipotent mesenchymal stromal (MMSC) and stellate liver cells (ZCP) in animals with partial hepatectomy.Materials and methods. The MMSC culture was isolated from the placental chorion of 5 laboratory animals f female mice aged 3-4 months, weighing 22-23 g, gestation period of 18 days. The mononuclear fraction of the cells was obtained by sequential mechanical and enzymatic treatment of the placental tissue. The cultivation of MMSCs was carried out in a CO2 incubator at a temperature of 37 0C with a carbon dioxide content of 5% and a humidity of 90%. ZCP was isolated by collagenase-pronase perfusion of the liver, followed by cell separation in the histodense density gradient. MMSCs of the 3rd passage were introduced, and ZKP was introduced immediately after isolation. MMSCs at a dose of 4 million cells/kg and ZCP at a dose of 9 million cells/ kg were used for transplantation to labotory animals. The cells were injected 1 hour after partial hepatectomy. The biochemical parameters of peripheral blood and morphometric parameters of the liver were evaluated on the 3rd, 7th day after the administration of MMSC.Results. As a result of the study, it was found that the combined transplantation of MMSC and ZCP after partial hepatectomy leads to the restoration of the level of enzymes that characterize cytolysis and cholestasis, normalization of the protein-synthetic function of the liver, normalization morphometric parameters of the liver. A significant mechanism for restoring the morphofunctional state of the liver can be considered the influence of transplanted MMSCs and ZCP on the cell repair system, which leads to a decrease in the severity of programmed cell death of hepatocytes and the level of pathological mitoses.Discussion. Combined transplantation of MMSCs and HCP after partial hepatectomy leads to an increase in the level of hepatocyte growth factor (HGF), thus contributing to an se in the mitotic activity of hepatocytes and the restoration of liver mass. The transplanted cells also, by increasing the activity of DNA repair enzymes of the PARP family, lead to a decrease in the level of pathological mitoses, inhibition of their programmed cell death.Conclusions. The conducted studies demonstrate the ability of combined MMSC and PCR transplantation to restore the morphofunctional state of the liver after partial hepatectomy and provide the basis for conducting pilot clinical studies

THE EFFECT OF MULTIPOTENT MESENCHYMAL STROMAL CELLS TRANSPLANTATION ON LIVER MORPHOMETRIC PARAMETERS OF MATURE AND OLD LABORATORY ANIMALS WITH TOXIC HEPATITIS

2020 ◽  
pp. 55-60
Author(s):  
И. Ю. Маклакова ◽  
Д. Ю. Гребнев ◽  
В. Ч. Юсупова ◽  
Е. М. Петрунина
Keyword(s):  
Mitotic Activity ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Toxic Hepatitis ◽  
Age Groups ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Morphometric Parameters ◽  
Laboratory Animals ◽  
Intracellular Regeneration ◽  
Hepatocyte Nucleus

Цель - изучение влияния трансплантации мультипотентных мезенхимальных стромальных клеток (ММСК) на морфометрические показатели печени зрелых и старых лабораторных животных в условиях токсического гепатита. Материал и методы. Эксперименты выполнены на зрелых и старых мышах-самцах. Токсический гепатит вызывали путем внутрибрюшинного введения CClв дозе 50 мкг/кг. Трансплантация клеток осуществлялась в хвостовую вену через 1 ч после введения четыреххлористого углерода однократно. Исследовалось влияние ММСК на морфометрические показатели печени в физиологических условиях и условиях токсического гепатита на 1-, 3-, 7-е сутки после трансплантации клеток. Результаты. У зрелых лабораторных животных на 3-и сутки после введения ММСК на фоне токсического гепатита обнаружено увеличение митотической активности, повышение количества гепатоцитов, площади ядра гепатоцитов и ядерноцитоплазматического индекса. В то же время, у старых лабораторных животных выявлено лишь увеличение площади ядра гепатоцитов и ядерно-цитоплазматического индекса. На 7-е сутки после введения ММСК на фоне токсического гепатита в обеих возрастных группах выявлены активация митотической активности, повышение количества гепатоцитов, увеличение площади ядра гепатоцитов и ядерно-цитоплазматического индекса. Выводы. Изменение морфометрических показателей печени у зрелых и старых лабораторных животных реализуется через механизмы как клеточной, так и внутриклеточной регенерации. При этом у старых лабораторных животных на 3-и сутки после введения ММСК выявлена активация лишь внутриклеточной регенерации, в то время как у зрелых лабораторных животных имеет место повышение клеточной и внутриклеточной регенерации гепатоцитов. В более поздние сроки в обеих изучаемых возрастных группах изменение основных морфометрических показателей печени реализуется через активацию как клеточной, так и внутриклеточной регенерации. Objective - to study the influence of multipotent mesenchymal stromal cells (MMSC) transplantation on morphometric parameters of the liver of mature and old laboratory animals with toxic hepatitis. Material and methods. The experiments were performed on mature and old male mice. Toxic hepatitis was caused by intraperitoneal administration of CCl4 at a dose of 50 μg/kg. The cells were transplanted via the tail vein 1 hour after administration of a single dose of carbon tetrachloride. The effect of MMSC on liver morphometric parameters in physiological conditions and after toxic hepatitis development was studied on days 1, 3, 7 after cell transplantation. Results. An increase in mitotic activity, an increase in the number of hepatocytes, hepatocyte nucleus area, and nuclear cytoplasmic index were found in mature laboratory animals with toxic hepatitis on the 3 day after the introduction of MMSC. At the same time, only an increase in the area of hepatocyte nucleus and nuclear cytoplasmic index was revealed in old laboratory animals. On the 7 day after the introduction of MMSC to the animals with toxic hepatitis, both age groups demonstrated activation of mitotic activity, an increase in the number of hepatocytes, an increase in the area of hepatocyte nucleus and nuclear cytoplasmic index. Conclusions. Changes in liver morphometric parameters in mature and old laboratory animals are realized through mechanisms of both cellular and intracellular regeneration. In addition, the activation of only intracellular regeneration was found in old laboratory animals on the 3rd day after the introduction of MMSC, while in mature laboratory animals there was an increase in cellular and intracellular regeneration of hepatocytes. In later periods in both studied age groups, the change in the main liver morphometric parameters is realized through the activation of both cellular and intracellular regeneration.

Programmed Cell Death Ligand 1 and Venous Thromboembolism in Patients with Primary Brain Tumors

2019 ◽  
Author(s):  
P. Seyed Mir ◽  
A.-S. Berghoff ◽  
M. Preusser ◽  
G. Ricken ◽  
J. Riedl ◽  
...  
Keyword(s):  
Cell Death ◽  
Venous Thromboembolism ◽  
Programmed Cell Death ◽  
Brain Tumors ◽  
Primary Brain Tumors

Glial cytotoxicity of low doses of cadmium as a model of heavy metal pollution influence on vertebrates

2020 ◽  
Vol 31 (1) ◽  
pp. 3-10
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Oxidative Damage ◽  
Cadmium Chloride ◽  
Glioma Cells ◽  
Low Doses ◽  
Genotoxic Effects ◽  
Cadmium Ions

Cadmium is a common transition metal that entails an extremely wide range of toxic effects in humans and animals. The cytotoxicity of cadmium ions and its compounds is due to various genotoxic effects, including both DNA damage and chromosomal aberrations. Some bone diseases, kidney and digestive system diseases are determined as pathologies that are closely associated with cadmium intoxication. In addition, cadmium is included in the list of carcinogens because of its ability to initiate the development of tumors of several forms of cancer under conditions of chronic or acute intoxication. Despite many studies of the effects of cadmium in animal models and cohorts of patients, in which cadmium effects has occurred, its molecular mechanisms of action are not fully understood. The genotoxic effects of cadmium and the induction of programmed cell death have attracted the attention of researchers in the last decade. In recent years, the results obtained for in vivo and in vitro experimental models have shown extremely high cytotoxicity of sublethal concentrations of cadmium and its compounds in various tissues. One of the most studied causes of cadmium cytotoxicity is the development of oxidative stress and associated oxidative damage to macromolecules of lipids, proteins and nucleic acids. Brain cells are most sensitive to oxidative damage and can be a critical target of cadmium cytotoxicity. Thus, oxidative damage caused by cadmium can initiate genotoxicity, programmed cell death and inhibit their viability in the human and animal brains. To test our hypothesis, cadmium cytotoxicity was assessed in vivo in U251 glioma cells through viability determinants and markers of oxidative stress and apoptosis. The result of the cell viability analysis showed the dose-dependent action of cadmium chloride in glioma cells, as well as the generation of oxidative stress (p <0.05). Calculated for 48 hours of exposure, the LD50 was 3.1 μg×ml-1. The rates of apoptotic death of glioma cells also progressively increased depending on the dose of cadmium ions. A high correlation between cadmium concentration and apoptotic response (p <0.01) was found for cells exposed to 3–4 μg×ml-1 cadmium chloride. Moreover, a significant correlation was found between oxidative stress (lipid peroxidation) and induction of apoptosis. The results indicate a strong relationship between the generation of oxidative damage by macromolecules and the initiation of programmed cell death in glial cells under conditions of low doses of cadmium chloride. The presented results show that cadmium ions can induce oxidative damage in brain cells and inhibit their viability through the induction of programmed death. Such effects of cadmium intoxication can be considered as a model of the impact of heavy metal pollution on vertebrates.

Dynamical analysis of the programmed cell death pathway

2007 ◽  
Author(s):  
Luciano Carotenuto ◽  
Vincenza Pace ◽  
Dina Bellizzi ◽  
Giovanna De Benedictis
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dynamical Analysis ◽  
Cell Death Pathway

Biological response of the organism to the introduction of metal nanocomposites

2020 ◽  
pp. 761-762
Author(s):  
L. M. Sosedova ◽  
V. S. Rukavishnikov ◽  
E. A. Titov
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Biological Response ◽  
Brain Cell ◽  
Metal Nanocomposites ◽  
The Brain

The results of a study on rats toxicity of nanoparticles of metals bismuth, gadolinium and silver encapsulated in a natural biopolymer matrix arabinogalactan are presented. When intake of nanocomposite of silver revealed the readiness of the brain cell to apoptosis. The effect of bismuth and gadolinium nanocomposites did not cause an increase in the process of programmed cell death.

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