title: Human cord blood CD34+ cells develop into hepatocytes in the livers of NOD/SCID/gamma(c)null mice through cell fusion.
abstract: Several studies have shown that hepatocytes can be generated from hematopoietic stem cells, but this event is believed to be rare and to require hepatic damage. To investigate this phenomenon in human cells, we used a NOD/SCID/gamma(c)null (NOG) mouse model that can achieve a tremendously high level of chimerism when transplanted with human hematopoietic cells. Even without hepatotoxic treatment other than irradiation, human albumin and alpha-1-antitrypsin-positive cells were invariably detected in the livers of NOG mice after i.v. transplantation of human cord blood CD34+ cells. Human albumin was detected in the murine sera, indicating functional maturation of the human hepatocytes. Flow cytometric analysis of recipient liver cells in single-cell suspension demonstrated that human albumin-positive cells were also positive for both murine and human MHC and were negative for human CD45. PCR analysis of recipient livers revealed the expression of a wide variety of human hepatocyte- or cholangiocyte-specific mRNAs. These results show that human CD34+ cells fuse with hepatocytes of NOG mice without liver injury, lose their hematopoietic phenotype, and begin hepatocyte-specific gene transcription. These phenomena were not observed when CD34- cells were transplanted. Thus, our model revealed a previously unidentified pathway of human hematopoietic stem/progenitor cell differentiation.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Fujino
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Hiramatsu
authors.forename: Atsunori
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: Akira
authors.initials: A
authors.lastname: Niwa
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Noma
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Shiota
authors.forename: Katsutsugu
authors.initials: K
authors.lastname: Umeda
authors.forename: Momoko
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology*; D001483:Base Sequence; D002459:Cell Fusion; D019070:Cell Lineage; D017690:Cell Transplantation; D017931:DNA Primers; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018952:Antigens, CD34; D017931:DNA Primers