Search results for "hepatocyte differentiation"
showing 10 items of 10 documents
Recent patents and advances in hepatocyte-like cells differentiation by mesenchymal stem cells
2013
Chronic liver diseases constitute one of the main causes of death in western countries. Orthotopic liver transplantation still remains the final therapeutic approach to these diseases, but alternative therapeutic strategies are actively researched. Hepatocyte transplantation is considered a promising approach, even if this technique presents many limitations. These factors boosted the research for alternative cell sources to derive functional hepatocytes. In the last years, research on basic biology and differentiative ability of adult, embryonic and perinatal stem cells has constantly increased. The term "perinatal" indicates stem cell populations derived from foetal sources such as placen…
Sequential Hepatogenic Transdifferentiation of Adipose Tissue-Derived Stem Cells: Relevance of Different Extracellular Signaling Molecules, Transcrip…
2009
Adipose tissue contains a mesenchymal stein cell (MSC) population Known as adipose-derived stein cells (ASCs) capable of differentiating into different cell types. Our aim was to induce hepatic transdifferentiation of ASCs by sequential exposure to several combinations of cytokines, growth factors, and hormones. The most efficient hepatogenic protocol includes fibroblastic growth factors (FGF) 2 and 4 and epidermal growth factor (EGF) (step 1), hepatocyte growth factor (HGF), FGF2, FGF4, and nicotinamide (Nic) (step 2), and oncostatin M (OSM), dexamethasone (Dex), and insulin-tranferrin-selenium (step 3). This protocol activated transcription factors [GATA6, Hex, CCAAT/enhancer binding prot…
Recent Advances in Derivation of Functional Hepatocytes from Placental Stem Cells
2013
Abstract: End-stage liver diseases are one of the leading causes of death in the world. Often orthotopic liver transplantation represents the final therapeutic choice. The limits of this approach are the scarcity of donor livers available, and the many side effects related to the administration of immune suppressants to the patients. Cellular therapy for liver diseases is increasingly being viewed as a promising strategy to provide hepatocytes to replenish the parenchymal cells of the organ. This technique suffers of some important limitations, such as the difficulty in isolating sufficient cell numbers (e.g. when adult or foetal hepatocytes are used for transplantation), the limited viabil…
Human Wharton's jelly-derived mesenchymal stem cells express several immunomodulatory molecules both in their naïve state and hepatocyte-like differe…
2011
Wharton’s jelly (WJ), the main constituent of umbilical cord, is a reliable source of mesenchymal stem cells (MSC). WJ-MSC show unique ability in crossing lineage borders. As other extraembryonic mesenchymal populations (placenta and amnionderived cells), WJ-MSC express several immunomodulatory molecules, essential during the initial phases of human development. Indeed, our recent work pointed out the expression of non-classical HLA molecules as HLA-G in such cells, together with a favorable combination of B7 costimulators. Very few data in literature suggest that some of the immune features of the naïve cells are maintained after performing differentiation. The aim of this work was extendi…
An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite reg…
2011
Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biological processes might provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene HNF4α, directly represses the expression of the epithelial microRNAs (miRs)-200c and-34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4α, p…
The stable repression of mesenchymal program is required for hepatocyte identity: A novel role for hepatocyte nuclear factor 4α
2011
The concept that cellular terminal differentiation is stably maintained once development is complete has been questioned by numerous observations showing that differentiated epithelium may undergo an epithelial-to-mesenchymal transition (EMT) program. EMT and the reverse process, mesenchymal-to-epithelial transition (MET), are typical events of development, tissue repair, and tumor progression. In this study, we aimed to clarify the molecular mechanisms underlying these phenotypic conversions in hepatocytes. Hepatocyte nuclear factor 4α (HNF4α) was overexpressed in different hepatocyte cell lines and the resulting gene expression profile was determined by real-time quantitative polymerase…
SILAC labeling coupled to shotgun proteomics analysis of membrane proteins of liver stem/hepatocyte allows to candidate the inhibition of TGF-beta pa…
2014
Background: Despite extensive research on hepatic cells precursors and their differentiated states, much remains to be learned about the mechanism underlying the self-renewal and differentiation.Results: We apply the SILAC (stable isotope labeling by amino acids in cell culture) approach to quantitatively compare the membrane proteome of the resident liver stem cells (RLSCs) and their progeny spontaneously differentiated into epithelial/hepatocyte (RLSCdH). By means of nanoLC-MALDI-TOF/TOF approach, we identified and quantified 248 membrane proteins and 57 of them were found modulated during hepatocyte differentiation. Functional clustering of differentially expressed proteins by Ingenuity …
Non-classical type I HLAs and B7 costimulators revisited: analysis of expression and immunomodulatory role in undifferentiated and differentiated MSC…
2011
Introduction. Wharton’s jelly (WJ), the main constituent of umbilical cord, emerged as a reliable and uncontroversial source of mesenchymal stem cells (MSC). WJ-MSC show unique ability in crossing lineage borders, therefore being capable to trans-ifferentiate towards mature cytotypes derived from the three germ layers. As other fetal-associated cells, WJ-MSC express several immunomodulatory molecules, essential during the initial phases of human development and for the processes linked to the tolerance of the mother to the semiallogeneic embryo. Very few data are present in literature on the maintenance of the immune privilege of the naïve cells after performing differentiation. Our previou…
Wharton’s jelly mesenchymal stem cells differentiation into hepatocyte-like cells: functional characterization and expression of immunomodulatory mol…
2015
Mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs) recently emerged as promising tools for cellular therapy due to their ability to differentiate into diverse cell types and their immunomodulatory features. Little is known on the expression of immunomodulatory molecules in mature cells differentiated from WJ-MSCs, therefore we aimed to characterize the extent of maintenance of the naive traits of these cells also in a highly specialized differentiated counterpart. WJ-MSCs were differentiated into hepatocyte-like cells (HLCs) with a four weeks protocol. RT-PCR, flow cytometry, IHC and ICC were performed to assess expression of key markers in both undifferentiated and differentiate…
Functional inhibition of Oct leads to HNF4α upregulation
2021
Organic cation transporters (human, OCT; mouse, Oct) are responsible for the intracellular uptake and detoxification of a broad spectrum of endogenous and exogenous substrates. The OCT1 gene SLC22A1 (human; mouse, Scl22a1) is transactivated by hepatocyte nuclear factor 4α (human, HNF4α; mouse, Hnf4α). HNF4α is a master regulator of hepatocyte differentiation and is frequently associated with hepatocellular carcinoma (HCC). In addition, the downregulation of HNF4α is associated with enhanced fibrogenesis. Our recent study revealed that hepatocarcinogenesis and fibrosis were enhanced with the loss of Oct3 (gene, Slc22a3). Notably, differences in Hnf4α expression, and in cholestasis and fibros…