Hepatic stellate cells - Regional stem cells of the liver or a component of microenvironment?

For years, it is debated about the nature and localization of stem cell of the liver. In recent years, a particular interest is paid to hepatic stellate cells. According to the conducted researches, these cells are actively involved in restoring of hepatocytes population by different liver damages and they have a number of properties specific to stem cells. It should be noted that hepatic stellate cells are able to maintain viability in culture and differentiate into hepatocyte direction under certain conditions in vitro. Interestingly, hepatic stellate cells may themselves create such conditions for progenitor cells in vivo, as well as in vitro. This is achieved thanks to the hepatic stellate cells secretion of the extracellular matrix proteins, a complex of growth factors and establishment of direct intercellular contacts. Stellate cells, localized in perisinusoidal space, are also influenced by the surrounding hepatocytes and endothelial cells. Thus, perisinusoidal space is a kind of dynamic system, in which hepatocytes and endothelial cells determine the "resting" state of stellate cells, and the latter, if necessary, can be activated and participate in restoration of the liver cell populations. Based on these data, the researchers suggest that the hepatic perisinusoidal space - a niche of hepatic stellate cells, regional stem cells of the liver

Serum Cytokine Levels and Their Relation to Clinical Features in Patients with Autoimmune Liver Diseases

Serum cytokine levels were explored in a combined group of patients with autoimmune liver diseases (AILDs) and separately in patients with autoimmune hepatitis (AIH) and overlap syndrome. Overall, 60 patients with AILD, among them 32 patients with AIH and 28 patients with overlap syndrome, were included in the cross-sectional study. Serum cytokine levels were measured at baseline and compared to those of 21 healthy controls. Patients with AILD had significantly higher levels of IL-6 (0.70 (range 0.17-99.86) in patients with AILD compared to 0.40 (range 0.14-2.65) in controls, p < 0.01), IL-8 (1.66 (0.45-34.58) versus 0.53 (0.35-2.38), resp., p < 0.01), and TNF-α (2.61 (0.23-120.88) versus 1.65 (0.21-7.54), resp., p < 0.01). Adjusted logistic regression analysis revealed a pronounced relation of IL-8 and AILD, 48.36 (3.63-643.60), as well as AIH, 18.54 (1.08-318.54), and overlap syndrome, 23.85 (2.37-240.23), while the associations between the level of other cytokines and AILD were assessed as nonsignificant. In the language of absolute numbers, the increase of IL-8 serum level by 1 pg/mL had increased the chance for a patient to find himself in a group of AILD by 48.36 times. Also, high IL-8 serum levels were strongly related to clinical parameters

The effect of oxygen concentration on embryo development and assisted reproductive technologies efficiency

© 2018 Human Stem Cell Institute. All rights reserved. Many different factors have an effect on the preimplantation development of embryos under conditions in vitro. One of these factors is the oxygen concentration in the culture medium. Currently, IVF labs have ability to cultivate embryos either under conditions of atmospheric oxygen concentration or at low oxygen concentration (hypoxia). This review is focused on the analysis of up to date research and clinical results which are trying to establish an "optimal" composition of the gas mixture in the incubator to generate more viable embryos and increase the effectiveness of assisted reproductive technologies programs

Influence of the human umbilical cord blood mononuclear cells transplantation on regeneration of the rat kidney after unilateral ureteral obstruction

Stem cell therapy may provide effective and patogenetically proved treatment of chronic kidney disease caused by interstitial fibrosis after tubule damage. It was reported that transplanted bone marrow stem cells participate in tubule regeneration [1]. At the same time the potential of hematopoietic stem cells in tubule regeneration is not well investigated. The purpose of the study was to evaluate the participation of human cord blood stem cells in rat kidney tubule regeneration after unilateral ureteral obstruction. 18 laboratory rats were subjected to left unilateral ureteral obstruction (UUO). 3×106 of human cord blood mononuclears (n = 9) or equivalent volume of saline (n = 9) were injected into rat's tail vein. Kidney tissue was collected at the end of the 3, 6 or 14 day after operation. Paraffin-embedded slices were stained with mononuclear antibodies against c-kit (stem and progenitor cell marker), proliferating cell nuclear antigen for the cells proliferative capacity evaluation (PCNA) and α-smooth muscle actin (α-SMA) for myofibroblasts detection. Number of proliferating cells in tubuli ad interstitium was considerably larger in the obstructed kidney of the transplantation group, as well as the number of proliferating cells in the glomeruli at 14 day after operation. At the same time number of α-SMA-positive cells in the transplanted group was significantly lower compared with sham-transplanted group. There were no differences in expression of these markers in the contralateral kidneys. UUO had no impact on c-kit expression in kidney tissue. Thus, transplantation of human cord blood mononuclear cells in UUO stimulates proliferative activity of tubular cells and interstitium, reduces myofibroblast activation and risk of kidney fibrosis. © Human stem cells institute, 2013

C-kit and desmin-positive cells in expression in islets of pancreas during alloxan diabetes in rats.

Nowadays there are findings that C-kit-positive and desmin-positive stellate cells help to regenerate endocrine part of pancreas. But still it is unknown about their role and the way of differentiation of these cells during pancreas regeneration. That's why the aim of our work was to study the dynamic of these cells population during alloxan diabetes in rats. The work was made on 33 rats with experimental diabetes. Blood glucose, insulin and glucagon levels were analyzed. Also the expression of desmin (marker of stellate cells), α-SMA (marker of myofibroblast), C-kit (marker of endocrine stem cells), insulin and glucagon (marker of differentiated α- And β-cells of Langerhans islets) was studied. The expression of desmin was found after one day of experimental diabetes in islets cells of pancreas. Maximum of these cells was after the third day of the experiment. Also after one day of the experiment C-kit-positive cells, which expressed insulin and glucagon were found. We suppose that stellate cells are the main factor of microenvironment for differentiation of C-kit-positive progenitor cells into β-cells through the stage of glucagon-positive cells because stellate pancreas cells can produce different growth factors and components of intercellular matrics. © Human stem cells institute, 2013

C-kit-positive progenitor cells activation in rats pancreas after partial hepatectomy

One of the most common markers of pancreas stem cells is a stem cell factor receptor C-kit. According to some authors, this marker is presented in islet cells of normal rat pancreas. But it is unknown about the behavior of these cells in disorders of carbohydrate metabolism during liver disease. The aim of our study was to evaluate C-kit expression in pancreas after partial hepatectomy in rats. Partial hepatectomy was performed for 27 white male rats. The expression of C-kit, insulin and glucagon in rats pancreas was studied. The expression of C-kit in islets and interstitial cells was shown in results after 3 days of the experiment, and double staining showed that these cells can express glucagon. Thus, there is the activation of C-kit+ progenitor cells in pancreas after partial hepatectomy and the beginning of there differentiation to α-cells of Langerhance islets

Population Dynamics of MafA-Positive Cells During Ontogeny of Human Pancreas

© 2016, Springer Science+Business Media New York.Diverse transcription factors influencing cell differentiation are often chosen as markers of β cell progenitors. One of these transcription factors is MafA, which according to data in literature activates the expression of insulin gene in β cells. Other data support the hypothesis that MafA is required solely for the regulation of insulin secretion by β cells of adult islets and is not involved in the development of islet cells. In this paper, we study the role of MafA through both examination of human pancreas ontogeny and comparison of these data with dynamic changes in the population of insulin-positive and glucagon-positive cells. The aim of this research was the immunohistochemical analysis of MafA, insulin, and glucagon expression during human pancreas ontogeny. The research was conducted on whole embryos and isolated human fetal organs, obtained as a result of either miscarriage or legal medical abortion with voluntary consent of patients, and also on autopsy material from infant and adult human pancreas. As a result of this study, it was found that, during the ontogeny of human pancreas, the first MafA-positive cells appear in the islets at 12.5 weeks of gestation, that is, later than both insulin-positive cells (11.5 weeks of gestation) and glucagon-positive cells (8.5 weeks of gestation). No MafA-positive cells were found in the epithelium of pancreatic ducts. The number of MafA-positive cells in the islets increases during pancreatic organogenesis. The results of our research do not allow us to regard MafA as a marker of undifferentiated progenitors of islet cells. Based on this, we believe that the results obtained in this study are a supplementary contribution to the hypothesis that relates MafA to the markers of adult β cells

Changes of liver microstructure after partial hepatectomy in rats

Ability of mammalian liver to regenerate is one of the favorite examples of "regenerative medicine". At the same time liver regeneration can not be viewed as a simple hypertrophy, it must have some appropriate steps. Understanding of these processes is crucial for correct interpretation of liver therapy results, especially after cellular therapy. But, unfortunately, original and first-hand data regarding changes in liver microstructure during regeneration is relatively scarce. This work was dedicated to study changes of liver microstructure during liver regeneration after partial hepatectomy in rats. We analyzed proliferative processes, perisinusoidal cells involvement, sizes of classical hepatic lobules, participation of bile ducts, branches of afferent and efferent hepatic vessels in liver regeneration on 1, 2, 3, 5, 7 postoperative days. Our results have shown that liver microstructure during regeneration after partial hepatectomy undergoes two stages: hypertrophy of hepatic lobules by proliferation of liver cells until 4th day and division of hepatic lobules by branching of bile ducts, hepatic artery, portal and central veins from 4th until 7th postoperative day. © Human stem cells institute, 2013

Selaginella bryopteris

The effective long-term cryopreservation of human mesenchymal stem cells (MSCs) is an essential prerequisite step and represents a critical approach for their sustained supply in basic research, regenerative medicine, and tissue engineering applications. Therefore, attempts have been made in the present investigation to formulate a freezing solution consisting of a combination of Selaginella bryopteris water-soluble extract with and without dimethyl sulfoxide (Me2SO) for the efficient long-term storage of human umbilical cord blood- (hUCB-) derived MSCs. The cryopreservation experiment using the formulated freezing solution was further performed with hUCB MSCs in a controlled rate freezer. A significant increase in postthaw cell viability and cell attachment of MSCs was achieved with freezing medium containing Selaginella bryopteris water extract along with 10% Me2SO as compared to the freezing medium containing Me2SO (10% v/v) alone. Furthermore, the decreasing apoptotic events and reactive oxygen species production along with increasing expression of heat shock proteins also confirmed the beneficial effect of Selaginella bryopteris water extract. The beneficial effect of Selaginella bryopteris water extract was validated by its ability to render postpreservation high cell viability. In conclusion, the formulated freezing solution has been demonstrated to be effective for the standardization of cryopreservation protocol for hMSCs

C-kit-positive pancreas islets cell of rats pancreas as a endocrine cells progenitor during alloxan diabetes

One of the most common markers for stem cells in pancreas is the stem cell factor receptor C-kit (CD117) that plays a main role in differentiation of progenitor endocrine cells of pancreas islets in prenatal development and persists after birth. But still the role of C-kit positive cells in islet β-cells regeneration during the diabetes mellitus type I has not been studied. That's why the aim of our work was to study the dynamic of C-kit expression in the pancreas islets during the experimental alloxan diabetes in rats. The work was made on 33 rats with the experimental diabetes. Blood glucose levels, levels of insulin and glucagon were measured. And also we studied the expression of C-kit, insulin and glucagon in rat pancreas. The results of the study showed the C-kit expression after one day of the experimental hyperglycemia. These cells were also expressed insulin and glucagon. We suppose that C-kit+-cells, which produce insulin, were enable to correct disrupted carbohydrate metabolism during alloxan diabetes