title: Self-formation of vascularized hepatic tissue from human adult hepatocyte.
abstract: BACKGROUND
  Recent study has demonstrated the important role of endothelial-mesenchymal interactions in 3-dimensional self-organization of immature progenitor populations with the use of mimicking of organogenesis. Here, we show that the same principle can be applicable to adult mature cells, ie, human adult hepatocytes (hAHs).
  
  
  METHODS
  We cultivated hAHs with fluorescence-labeled human mesenchymal cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) in micro-well culture plates and observed them for 9 days. Fluorescence microscopy imaging analyses were performed to evaluate the internal structures of generated 3-dimensional tissues. Maintenance of in vitro protein production capacity was examined with the use of enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  hAHs started to self-organize into 3-dimensional tissue with the use of coculturing with hMSCs and HUVECs. Live imaging analyses showed that endothelial cells started sprouting inside the generated tissues after 2 days of culture. ELISA showed that human albumin production capacity was improved with the use of coculture compared with hAHs-only culture after 9 days.
  
  
  CONCLUSIONS
  We demonstrated that 3-dimensional vascularized hepatic tissue could be generated from hAHs by reconstituting endothelial-mesenchymal interactions. Future studies are needed to evaluate the therapeutic potential of vascularized hepatic tissue transplantation, and this may pave a new way to establish a new transplantation modality as an alternative to hepatocyte transplantation.
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Enomoto
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Enomura
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Project Leader of Advanced Medical Research Center, Yokohama City University, Yokohama, Japan; PRESTO, Japan Science and Technology Agency, Kawaguchi, Japan. Electronic address: ttakebe@yokohama-cu.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Takebe
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mitsuhashi
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Yoshizawa
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Project Leader of Advanced Medical Research Center, Yokohama City University, Yokohama, Japan. Electronic address: rtanigu@med.yokohama-cu.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Taniguchi
mesh_terms: D000328:Adult; D021522:Bioartificial Organs; D002450:Cell Communication; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000098:blood supply* / Q000166:cytology* / Q000378:metabolism; D016031:Liver Transplantation / Q000379:methods; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008648:Mesoderm / Q000166:cytology; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic; D012709:Serum Albumin / Q000378:metabolism; D000075462:Serum Albumin, Human; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D014162:Transfection; D000097573:Red Fluorescent Protein
chemical_list: D008164:Luminescent Proteins; D012709:Serum Albumin; D000075462:Serum Albumin, Human; D000097573:Red Fluorescent Protein; C422455:ALB protein, human