Pharmacological modulation of cell functional activity with valproic acid and erythropoietin

Abstract

Introduction: Valproic acid (VA) is carboxylic acid with a branched chain, which is used as an antiepileptic drug. Valproic acid influence on cells in vivo: VA, which is an antiepileptic drug, is also a teratogen, which causes defects of a neural tube and an axial skeleton, although the mechanisms are not yet fully clear. Valproic acid influence on mesenchymal stem cells (MSC) in vitro: It is shown that valproic acid reduces the intracellular level of oxygen active forms. Valproic acid effect on tumor cells: VA inhibits tumor growth through several mechanisms, including the cell cycle stop, differentiation induction and inhibition of growth of tumor vessels. Valproic acid influence on enzymes: It affects mainly GSK-3. Valproic acid influence on animals’ cells: It is shown that VA can significantly improve an ability to develop in vitro and improve nuclear reprogramming of embryos. Erythropoietin (EPO): Is an hypoxia-induced hormone and a cytokine, which is necessary for normal erythropoiesis. EPO is widely used in in vitro experiments. Conclusion: Thus, the influence of VA and EPO on cells can be used in cell technologies.

Conditioned Medium of Induced Mesenchymal Stem Cells as an Activator of Differentiation in The Osteogenic Direction

“…c at a temperature of 20 ° C. For the hydrolytic digestion of the protein, trypsin was used in an enzyme / total protein weight ratio of 1/50 and incubated overnight at 37 °C. The resulting mixture of peptides was dried in a centrifugal concentrator at 45 ° C for 30 min, the peptides were redissolved in 20 μ L of 0.1% formic acid and subjected to further mass spectrometric analysis 7,8 . Proteomic analysis of peptides was carried out using an Ultimate 3000 RSLCnano chromatographic HPLC system (Thermo Scientific, USA) connected to a Q-exactive HFX mass spectrometer (Thermo Scientific, USA) [13][14][15][16][17] .…”

“…During the annotation, a functional analysis algorithm was used to identify statistically significant representation of certain groups of proteins among all genes / proteins in the sample under study. The statistical significance was assessed using the probability p-value, as well as the Adjusted P-value, which was calculated taking into account the multiplicity of comparison [7][8][9][10][11][12][13] . The groups for which the Adjusted P-value was less than 0.001 were considered significant protein groups in the classifications.…”

“…Mesenchymal stem cells are regarded as multipotent adult stem cells in multiple tissues, such as the fat tissue, umbilical cord, as well as bone marrow 5, 6 . Mesenchymal stem cells are able to self-renew through dividing and may differentiate into numerous tissues, such as bone, cartilage, muscle and fat cells, and connective tissue 7, 8 . Mesenchymal stem cells (MSCs) have a wide range of properties, including multipotency, high proliferative activity, and differentiation potential.…”

“…They secrete a complex of bioactive substances -a secret: cytokines, chemokines, adhesion molecules, lipid mediators, growth factors, hormones, vesicles. Mesenchymal stem cells are relatively easily isolated and cultured in a laboratory, where they are used to obtain cell products and as experimental models [6][7][8][9] . Recently, evidence has accumulated supporting the effectiveness of the MSC-conditioned medium (CM) in studies aimed at assessing therapeutic potential 10, 11 .…”