Wnt/beta-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma ...or hepatoblastoma. The present study evaluated the role of Wnt/beta-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, beta-catenin nuclear translocation, up-regulation of genes related to the Wnt/beta-catenin pathway, such as Lrp5 and Fzd3, as well as the oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/beta-catenin inactivation. Hepatocytes with nuclear translocation of beta-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans isomerase A or lactate dehydrogenase beta-chain were up-regulated only with the protocol associated with Wnt signaling activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin beta-chain were down-regulated in this protocol. In conclusion, our results suggest that activation of the Wnt/beta-catenin pathway during human mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype.
It is unknown if the beneficial effects of mesenchymal stromal cells (MSC) transplantation into the liver are dependent on their anchorage and differentiation into hepatocytes or rather the result of ...the release of stem cell intracellular content with hepatoprotector properties.
The effects of intact MSC transplantation were compared with the infusion of MSC lysates in an experimental rat model of acute liver failure.
A more powerful hepatoprotective and antiapoptotic effect was obtained after infusion of MSC lysates than intact MSC. Changes in IL-6 levels and miRNAs might explain the beneficial effects of MSC lysates.
Infusion of MSC lysates show a better hepatoprotective effect than the transplantation of intact MSC.
Background
The involvement of bone marrow hematopoietic stem cells (BMHSC) mobilization during liver regeneration from hepatectomized patients is under debate. The main aim of this study was to ...investigate the role of BMHSC mobilization after hepatic resection in 33 patients with liver disease.
Methods and Results
Mobilization of CD34
+
BMHSC after 72 h of surgery was found in peripheral blood of some, but not all, of the hepatectomized patients. These CD34
+
cells co-expressed other stem cells markers. The patients without BMHSC mobilization showed high levels of circulating and liver tissue BMHSC (CD34
+
cells) previous to surgery. Therefore, two types of patients: “mobilizers” and “non-mobilizers” were distinguished based on the values of CD34
+
cells before and after surgery. Changes in cytokines involved in the hepatic regeneration (HGF and TGF-β), and in BMHSC mobilization process (SCF, SDF-1, IL-12, or MMP-2), were detected in both groups. In addition, a higher activation previous to surgery of the SDF-1/CXCR4 axis in liver tissue was observed in non mobilizers patients compared to mobilizer patients.
Conclusion
BMHSC mobilization seems to be associated with variations in the levels of cytokines and proteolytic enzymes involved in hepatic regeneration and bone marrow matrix degradation. Hepatectomy may be an insufficient stimulus for BMSHC mobilization. The pre-hepatectomy higher levels CD34
+
cells in peripheral blood and liver, associated to the activation of hepatic SDF-1/CXCR4 axis, suggest a BMHSC mobilization process previous to surgery in non mobilizer patients.
Melatonin and
S-adenosyl-
l-methionine (SAMe) prevent oxidative stress and tissue dysfunction in obstructive jaundice (OJ). Lipid peroxidation is exacerbated in the presence of trace amounts of iron ...(Fe). The study investigated the regulation by melatonin and SAMe the induction of oxidative stress, iron metabolism disturbances and tissue injury in an experimental model of OJ. Different parameters of lipid peroxidation, antioxidant status, tissue injury and Fe metabolism were determined in liver and blood. OJ induced Fe accumulation in liver, and increased transferrin (Tf) saturation and loosely bound Fe content in blood. Melatonin, and SAMe at lesser extent, enhanced protein Tf content in liver and blood, that reduced loosely bound Fe content in blood. Melatonin and SAMe did not affect ferritin (FT) and Tf mRNA expression, but reduced Tf receptor (TfR) mRNA expression in liver. In conclusion, the effect of melatonin and SAMe on Fe metabolism may be included in the beneficial properties of these agents on lipid peroxidation and tissue injury induced by OJ.
Ovarian hormone depletion in ovariectomized experimental animals is a useful model with which to study the physiopathological consequences of menopause in women. It has been suggested that menopause ...is a risk factor for the induction of several cardiovascular disorders. In the present study we analyzed the effects of ovarian hormone depletion by ovariectomy (OVX) in a model of oxidative stress and cardiopathy induced by adriamycin (AD). To evaluate these effects, we measured parameters related to cardiac damage (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase) and oxidative stress (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione, nitric oxide and carbonyl proteins) in cardiac tissue and erythrocytes. OVX was found to alter all markers of oxidative stress and cell damage in cardiac tissue. Similarly, the OVX-derived loss of ovarian hormones enhanced cardiac damage and oxidative stress induced by AD. Our results suggest that antioxidant status in cardiac tissue and erythrocytes is seriously compromised by OVX during the cardiomyopathy induced by AD in experimental animals. In conclusion, the absence of hormones caused by OVX or menopause may induce or accelerate pre-existing cardiovascular dysfunctions.
Ovarian hormone depletion in ovariectomized experimental animals is a useful model with which to study the physiopathological consequences of menopause in women. It has been suggested that menopause ...is a risk factor for the induction of several cardiovascular disorders. In the present study we analyzed the effects of ovarian hormone depletion by ovariectomy (OVX) in a model of oxidative stress and cardiopathy induced by adriamycin (AD). To evaluate these effects, we measured parameters related to cardiac damage (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase) and oxidative stress (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione, nitric oxide and carbonyl proteins) in cardiac tissue and erythrocytes. OVX was found to alter all markers of oxidative stress and cell damage in cardiac tissue. Similarly, the OVX-derived loss of ovarian hormones enhanced cardiac damage and oxidative stress induced by AD. Our results suggest that antioxidant status in cardiac tissue and erythrocytes is seriously compromised by OVX during the cardiomyopathy induced by AD in experimental animals. In conclusion, the absence of hormones caused by OVX or menopause may induce or accelerate pre-existing cardiovascular dysfunctions.
Our work describes an optimised procedure for granulating nanometric and fine micrometric particles by spray-drying to achieve ready-to-print α-Al2O3 powders. The study started by identifying raw ...materials suited for the process through complete characterisation of particles shape, size, and surface properties. Then, dispersion in diluted and concentrated water-based suspensions was achieved thanks to polyethyleneimine and the effect of gradual dispersant addition was assessed by determining ζ potential and aggregates size variation. Suspensions rheology was studied and modelled through Krieger-Dougherty equation to identify the maximum solid loading allowing sufficient feeding through the spray-dryer nozzle. Finally, optimisation of the granulation conditions was performed.The procedure has allowed to achieve size distributions with D90 < 50 μm and Hausner ratio <1.3 ensuring sufficient flowability. The granulated powders were printed and the porosity evolution of the samples after sintering was studied by mercury intrusion porosimetry and SEM analysis.
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