title: Efficient endodermal induction of human adipose stem cells using various concentrations of Activin A for hepatic differentiation.
abstract: Activin A, which is a signaling molecule similar to Nodal, rapidly promotes endoderm induction of both embryonic stem (ES) cells and MSCs. Protocols for hepatic induction exhibit differences in efficiency and reproducibility depending on the specific methods or sources of MSCs. We characterized the effects of Activin A concentration on induction efficiency during hepatic differentiation of MSCs. Human MSCs (hMSCs) were differentiated into a hepatic lineage via a three-step protocol. Cells were first cultured in fetal bovine serum-free MSCs conditioned medium supplemented with Activin A (20, 50, or 100 ng/mL) for 3 days followed by treatment with additional agents. RT-PCR analysis, immunocytochemistry assays, periodic acid and Schiff's solution staining, and ELISAs were performed to confirm hepatic induction of hMSCs. Expression of genes related to the primitive foregut endoderm was observed in cells treated with higher concentration of Activin A. Gene expression related to functional primitive hepatocytes was observed in the early phases of hepatic differentiation. During the early period of the differentiation protocol, greater albumin secretion was observed when cells were treated with higher concentrations of Activin A.
  
  
  CONCLUSIONS
  Thus, Activin A concentration affects the rate of endoderm induction of hMSCs, and at higher concentrations in vitro.
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea; Graduate Program of Nano Science and Technology, Graduate School of Yonsei University, Seoul, Republic of Korea.
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea; Graduate Program of Nano Science and Technology, Graduate School of Yonsei University, Seoul, Republic of Korea.
authors.forename: Seon Ok
authors.initials: SO
authors.lastname: Min
authors.affiliation: Graduate Program of Nano Science and Technology, Graduate School of Yonsei University, Seoul, Republic of Korea.
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Bak
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: drhhk@yuhs.ac.
authors.forename: Ho Kyoung
authors.initials: HK
authors.lastname: Hwang
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea; Graduate Program of Nano Science and Technology, Graduate School of Yonsei University, Seoul, Republic of Korea; Cell Therapy Center, Severance Hospital, Seoul, Republic of Korea. Electronic address: kskim88@yuhs.ac.
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Kim
mesh_terms: D028341:Activins / Q000008:administration & dosage*; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004707:Endoderm / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
chemical_list: C422405:activin A; D028341:Activins
keywords: Activin A; Cell differentiation; Endoderm; Hepatocyte; Mesenchymal stem cells