title: Hepatic differentiation of human bone marrow-derived UE7T-13 cells: Effects of cytokines and CCN family gene expression.
abstract: OBJECTIVE
  Bone marrow-derived mesenchymal stem cells (MSC) are expected to be an excellent source of cells for transplantation. We aimed to study the culture conditions and involved genes to differentiate MSC into hepatocytes.
  
  
  METHODS
  The culture conditions to induce the efficient differentiation of human bone marrow-derived UE7T-13 cells were examined using cytokines, hormones, 5-azacytidine and type IV collagen.
  
  
  RESULTS
  We found that combination of acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) with type IV collagen coating induced hepatic differentiation of UE7T-13 cells at over 30% frequency, where expression of albumin mRNA was increased over 20-fold. The differentiated cells had functions of albumin production, glycogen synthesis and urea secretion as well as expressing hepatocyte-specific genes. In addition, these cellshave binuclear and cuboidal morphology, which is a characteristic feature of hepatocytes. During hepatic differentiation, UE7T-13 cells showed depressed expression of WISP1 and WISP2 genes, members of the CCN family. Conversely, knockdown of WISP1 or WISP2 gene by siRNA stimulated hepatic differentiation. The effect of aFGF/bFGF/HGF/type IV collagen coating and WISP1-siRNA on hepatic differentiation was additive.
  
  
  CONCLUSIONS
  The present study suggests that aFGF/bFGF/HGF/type IV collagen coating is the efficient condition for hepatic differentiation of UE7T-13 cells, and that WISP1 and WISP2 play an important role in hepatic transdifferentiation of these cells.
authors.affiliation: Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Tottori, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimomura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sakabe
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ishii
authors.forename: Kazue
authors.initials: K
authors.lastname: Gonda
authors.forename: Rie
authors.initials: R
authors.lastname: Murai
authors.forename: Kazuko
authors.initials: K
authors.lastname: Takubo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hoshikawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kurimasa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
authors.forename: Taro
authors.initials: T
authors.lastname: Uyama
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Goshi
authors.initials: G
authors.lastname: Shiota