title: Efficient generation of functional hepatocyte-like cells from menstrual blood-derived stem cells.
abstract: In recent years, the advantages of menstrual blood-derived stem cells (MenSCs), such as minimal ethical considerations, easy access and high proliferative ability, have inspired scientists to investigate the potential of MenSCs in cell therapy of different diseases. In order to characterize the potency of these cells for future cell therapy of liver diseases, we examined the potential of MenSCs to differentiate into hepatocytes, using different protocols. First, the immunophenotyping properties and potential of MenSCs to differentiate into osteoblasts, adipocytes and chondrocytes were evaluated. Thereafter, the differentiation protocols developed by two concentrations of hepatocyte growth factor (HGF) and oncostatin M (OSM), in combination with other components in serum-supplemented or serum-free culture media, were also investigated. The sequential differentiation was monitored by real-time PCR, immunostaining and functional assays. Our primary data revealed that the isolated MenSCs exhibited mesenchymal stem cell markers in parallel to OCT-4 as an embryonic marker. Regardless of differentiation procedures, the developed cells expressed mature hepatocyte markers, such as albumin, tyrosine aminotransferase and cytokeratin-18 at the mRNA and protein levels. They also showed functional properties of hepatocytes, including albumin secretion, glycogen storage and cytochrome P450 7A1 expression. However, the degree of differentiation was dependent on the concentrations of HGF and OSM. Indeed, omission of serum during the differentiation process caused typical improvement in hepatocyte-specific functions. This study is a novel report demonstrating the differentiation potential of MenSCs into hepatocyte-like cells. We recommend a complementary serum-free differentiation protocol for enrichment of in vitro production of functional MenSC-derived hepatocyte-like cells that could lead to a major step toward applied stem cell therapy of chronic liver diseases.
authors.affiliation: Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Sayeh
authors.initials: S
authors.lastname: Khanjani
authors.affiliation: Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Manijeh
authors.initials: M
authors.lastname: Khanmohammadi
authors.affiliation: Nanobiotechnology Research Centre, Avicenna Research Institute, ACECR, Tehran, Iran.|Immunology Research Centre, Tehran University of Medical Sciences, Iran.
authors.forename: Amir Hassan
authors.initials: AH
authors.lastname: Zarnani
authors.affiliation: Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Talebi
authors.affiliation: Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Haleh
authors.initials: H
authors.lastname: Edalatkhah
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Saman
authors.initials: S
authors.lastname: Eghtesad
authors.affiliation: Paramedical Faculty of Guilan, University of Medical Sciences, Langroud, Guilan, Iran.
authors.forename: Iraj
authors.initials: I
authors.lastname: Nikokar
authors.affiliation: Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Somaieh
authors.initials: S
authors.lastname: Kazemnejad
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000328:Adult; D000418:Albumins / Q000737:chemistry; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology; D003470:Culture Media / Q000737:chemistry; D016895:Culture Media, Serum-Free; D005260:Female; D005786:Gene Expression Regulation; D006003:Glycogen / Q000737:chemistry; D017228:Hepatocyte Growth Factor / Q000737:chemistry; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D053538:Keratin-18 / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000628:therapy; D008598:Menstruation / Q000097:blood*; D053683:Oncostatin M / Q000737:chemistry; D010006:Osteoblasts / Q000166:cytology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*
chemical_list: D000418:Albumins; D003470:Culture Media; D016895:Culture Media, Serum-Free; D053538:Keratin-18; D012333:RNA, Messenger; D053683:Oncostatin M; D017228:Hepatocyte Growth Factor; D006003:Glycogen
keywords: differentiation; hepatocyte; menstrual blood; stem cell