title: Menstrual blood-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells.
abstract: Orthotopic liver transplantation (OLT) is the only proven effective treatment for both end-stage and metabolic liver diseases. Hepatocyte transplantation is a promising alternative for OLT, but the lack of available donor livers has hampered its clinical application. Hepatocyte-like cells (HLCs) differentiated from many multi-potential stem cells can help repair damaged liver tissue. Yet almost suitable cells currently identified for human use are difficult to harvest and involve invasive procedures. Recently, a novel mesenchymal stem cell derived from human menstrual blood (MenSC) has been discovered and obtained easily and repeatedly. In this study, we examined whether the MenSCs are able to differentiate into functional HLCs in vitro. After three weeks of incubation in hepatogenic differentiation medium containing hepatocyte growth factor (HGF), fibroblast growth factor-4 (FGF-4), and oncostain M (OSM), cuboidal HLCs were observed, and cells also expressed hepatocyte-specific marker genes including albumin (ALB), α-fetoprotein (AFP), cytokeratin 18/19 (CK18/19), and cytochrome P450 1A1/3A4 (CYP1A1/3A4). Differentiated cells further demonstrated in vitro mature hepatocyte functions such as urea synthesis, glycogen storage, and indocyanine green (ICG) uptake. After intrasplenic transplantation into mice with 2/3 partial hepatectomy, the MenSC-derived HLCs were detected in recipient livers and expressed human ALB protein. We also showed that MenSC-derived HLC transplantation could restore the serum ALB level and significantly suppressed transaminase activity of liver injury animals. In conclusion, MenSCs may serve as an ideal, easily accessible source of material for tissue engineering and cell therapy of liver tissues.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Institute for Cell-Based Drug Development of Zhejiang Province, Hangzhou 310058, China; People's Hospital of Tongling, Tongling 244000, China; S-Evans Biosciences, Hangzhou 311121, China; The 117th Hospital of PLA, Hangzhou 310013, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Xiao-zhou
authors.initials: XZ
authors.lastname: Mou
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.forename: Jin-yang
authors.initials: JY
authors.lastname: Chen
authors.forename: Yi-fei
authors.initials: YF
authors.lastname: Li
authors.forename: Xiao-xing
authors.initials: XX
authors.lastname: Wu
authors.forename: Bing-yu
authors.initials: BY
authors.lastname: Xiang
authors.forename: Cai-yun
authors.initials: CY
authors.lastname: Li
authors.forename: Ju-ming
authors.initials: JM
authors.lastname: Ma
authors.forename: Charlie
authors.initials: C
authors.lastname: Xiang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation; D058625:End Stage Liver Disease / Q000628:therapy*; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation; D006801:Humans; D008297:Male; D008598:Menstruation / Q000097:blood*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C