Direct Differentiation of Homogeneous Human Adipose Stem Cells Into Functional Hepatocytes by Mimicking Liver Embryogenesis

摘要: The potential of adult human adipose tissue stem cells (hASCs) to differentiate into hepatocytes has generated much excitement over the possible use hASCs in therapeutic applications. An understanding molecular mechanisms that underlie plasticity toward will help make this possibility a reality. Herein, we show homogenous population characterized by high level CD73, CD90, and CD105 express pluripotent transcription factors OCT4, SOX2, NANOG, SALL4 under proliferation conditions. A activin allows for acquiring fate definitive endoderm (DE) expressing specific HEX, FOXA2, SOX17, GATA4 synchronously. Using reproducible three-stage method mimicking liver embryogenesis, were directed functional hepatocytes. In first stage, induced become DE 2 days cultured serum-free medium 3 treatment. Next, presence fibroblast growth factor (FGF) 4 bone morphogenetic protein (BMP) 5 efficient hepatic differentiation from cells. After 10 further maturated sequential exposure hepatocyte (HGF), oncostatin M (OSM), dexamethasone (DEX), hASC-derived expressed mature marker exhibited characterization, including albumin secretion, glycogen storage, urea production, activity drug transporters, cytochrome P450 activity. These findings be useful implementation purposes, metabolic analyses, toxicity screening, studies function. J. Cell. Physiol. 229: 801–812, 2014. © 2013 Wiley Periodicals, Inc.