[C-kit is a marker of human pancreatic endocrinocyte stem cells].

The aim of our study was to analyze the expression of one of the markers of progenitor cell of different cell types - CD 117 (C-kit) - in human pancreas during prenatal development. The pancreas of human embryos and fetuses at 4-28 weeks of gestation as well as of infants aged up to 2nd postnatal month, was studied. In histological sections, the immunocytochemical reactions were performed with the antibodies against C-kit, insulin and glucagon. In situ hybridization was used for detection of proinsulin mRNA. First cells expressing C-kit were found in human pancreas at 8.5 weeks of gestation among ductal epithelial cells. At 11.5 weeks of gestation these cells were found to segregate from the ductal epithelium and start to form islets. From 8.5 weeks of gestation C-kit positive cells started to express glucagon and proinsulin mRNA, and after 11.5 weeks they also expressed insulin. Islet C-kit positive cells coexpressing both glucagon and insulin, were also found after the birth. It may be concluded that C-kit positive endocrinocyte progenitor cells are common for pancreatic islet A- and B-cells and they are preserved in he islets after the birth.

[Cell sources of liver development].

The work is devoted to consequent expression of different cell types' protein markers such as vimentin, desmin, cytokeratins 7, 18, 19, stem cell markers CD34 and Bcl-2 at early stages of human prenatal development. Desmin was revealed in sinusoidal liver cells on 3.5-12 weeks of gestation, in mesenchymal cells of ventral mesentery and hepatoblasts on the 4-7 accordingly. During hepatic period of blood formation such desmin positive sinusoidal cells were found to be located close to blood cells. So called "cholangio-" cytokeratins 7 and 19 showed different expression, the first one was found only in cholangiocytes, while cytokeratin 19 existed in hepatoblasts as well until week 15-16 of prenatal development. Mesenchymal cells of ventral mesentery are positive for cytokeratins 18 and 19 even brighter than hepatoblasts in the 4-7 weeks of gestation. Bcl-2 expression was seen in the same periods in most sinusoidal and mesenchymal cells of ventral mesentery. CD34 positive cells are strongly depicted in liver sinusoids from 4th until 9th weeks of gestation, but probably they are not a source of hepatocytes' development in embryonic ontogenesis. Ventral mesentery mesenchyme was negative for this very marker. These results let us suppose that hepatocytes and cholangiocytes may develop from quite different embryonic sources: cholangyocytes grow exceptionally from duodenum epithelial cells, while there is a strong possibility that hepatoblasts formation occurs with participation of mesenchymal cells.

Mesenchymal-epithelial transformation of ito cells in vitro.

Cultured pure population of Ito cells isolated from adult rat liver expressed epithelial markers cytokeratin-8, alpha-fetoprotein, and gamma-glutamyl transpeptidase after forming a dense monolayer. Mesenchymal-epithelial transformation of these cells is possible, which suggests them as candidates of hepatic stem cells.

Alteration of the liver in rats with experimental dysbiosis.

We evaluated the relationship between pathological changes in the liver and the state of intestinal microflora in rats with experimental dysbiosis. Changes in the intestinal microflora were accompanied by alteration of the morphological structure in the liver. Enhanced proliferation of Ito cells served as an indirect evidence of damage to the liver. Ito cells did not undergo transformation into myofibroblasts that excluded the possibility of fibrosis.

[The Ito cells in ontogenesis and liver regeneration]. / Kletki Ito v ontogeneze i regeneratsii pecheni.

This review regards the Ito cells, which constitute one of the four types of liver sinusoidal cells. These cells synthesize many cytokines and extracellular matrix proteins. The Ito cells make an important link in retinoid metabolism. The role played by the Ito cells in liver hemopoiesis and differentiation of liver epithelium in prenatal ontogenesis is emphasized. The importance of the Ito cells in reparative liver regeneration is also discussed.

[The "direct mitogen" lead nitrate causes an intensification in lipid peroxidation and Ito cell activation in the rat liver]. / "Priamoi mitogen" nitrat svintsa vyzyvaet usilenie perekisnogo okisleniia lipidov i aktivatsiiu kletok Ito v pecheni krys.

We have used biochemical and immunohistochemical methods to study lipid peroxidation and activation of Ito cells in rat liver after a single administration of lead nitrate, a "direct mitogen". Lead nitrate was shown to injure hepatocytes through an increased lipid peroxidation. Response to the injury included increase in the proliferative activity of parenchymal and sinusoidal liver cells. In addition, activation of Ito cells has been noted, which manifested as increased expression of desmin and increased proliferation. However, no transformation of Ito cells into myofibroblasts has been observed. We discuss the possible role of Ito cell activation in creating conditions for the proliferation of liver parenchymal cells after the injury by lead nitrate.

[Cytokeratin expression in the pre- and postnatal ontogeny of the rat liver]. / Ekspressiia tsitokeratinov v pre- i postnatal'nom ontogeneze pecheni krys.

Expression of cytokeratins nos. 7 and 19 has been examined during pre- and postnatal ontogenesis in rat liver. Cells expressing cytokeratin no. 19 appeared around large incoming vessels in the liver at days 17-18 of gestation. From day 20 of gestation and during the first week of postnatal ontogenesis, cholangiocytes and periportal hepatocytes could be stained with antibodies against cytokeratin no. 19. The expression of cytokeratin no. 7 begins later than cytokeratin no. 19, and it is present only in cholangiocytes, throughout pre- and postnatal ontogenesis. Since pre- and postnatal hepatocytes are capable of expressing cytokeratin no. 19, we discuss possible use of this marker to study cytodifferentiation of epithelial cell lines in rat liver.