Recellularization of Rat Liver Scaffolds by Human Liver Stem Cells
Autor: | Navarro Tableros, Victor, HERRERA SANCHEZ, MARIA BEATRIZ, Figliolini, Federico, Romagnoli, Renato, Tetta, Ciro, Camussi, Giovanni, Herrera Sanchez, Maria Beatriz |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Homeobox protein NANOG
Fetal Proteins Male Nitrogen Cellular differentiation medicine.medical_treatment human liver stem cells Biomedical Engineering Bioengineering Apoptosis Biology Biochemistry Biomaterials Extracellular matrix Cytochrome P-450 Enzyme System Intermediate Filament Proteins Albumins medicine Cell Adhesion Animals Humans Urea Rats Wistar Fibroblast recellularization human liver stem cells Hepatocyte differentiation L-Lactate Dehydrogenase Tissue Scaffolds Growth factor Gene Expression Profiling Cell Differentiation recellularization Original Articles Cell biology Extracellular Matrix Rats Platelet Endothelial Cell Adhesion Molecule-1 Adult Stem Cells medicine.anatomical_structure Liver Hepatocyte Culture Media Conditioned Hepatocytes Stem cell Cell Division |
Popis: | In the present study, rat liver acellular scaffolds were used as biological support to guide the differentiation of human liver stem-like cells (HLSC) to hepatocytes. Once recellularized, the scaffolds were maintained for 21 days in different culture conditions to evaluate hepatocyte differentiation. HLSC lost the embryonic markers (alpha-fetoprotein, nestin, nanog, sox2, Musashi1, Oct 3/4, and pax2), increased the expression of albumin, and acquired the expression of lactate dehydrogenase and three subtypes of cytochrome P450. The presence of urea nitrogen in the culture medium confirmed their metabolic activity. In addition, cells attached to tubular remnant matrix structures expressed cytokeratin 19, CD31, and vimentin. The rat extracellular matrix (ECM) provides not only a favorable environment for differentiation of HLSC in functional hepatocytes (hepatocyte like) but also promoted the generation of some epithelial-like and endothelial-like cells. When fibroblast growth factor-epidermal growth factor or HLSC-derived conditioned medium was added to the perfusate, an improvement of survival rate was observed. The conditioned medium from HLSC potentiated also the metabolic activity of hepatocyte-like cells repopulating the acellular liver. In conclusion, HLSC have the potential, in association with the natural ECM, to generate in vitro a functional "humanized liver-like tissue." |
Databáze: | OpenAIRE |
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