Human cord blood CD34+ cells develop into hepatocytes in the livers of NOD/SCID/γcnull mice through cell fusion

Hisanori Fujino, Hidefumi Hiramatsu, Atsunori Tsuchiya, Akira Niwa, Haruyoshi Noma, Mitsutaka Shiota, Katsutsugu Umeda, Momoko Yoshimoto, Mamoru Ito, Toshio Heike, Tatsutoshi Nakahata

Research output: Contribution to journalArticle

38 Scopus citations

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/γcnull (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 α-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 hepatocytespecific 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.

Original languageEnglish (US)
Pages (from-to)3499-3510
Number of pages12
JournalFASEB Journal
Volume21
Issue number13
DOIs
StatePublished - Nov 1 2007

Keywords

  • Bone marrow-derived cell
  • Hematopoietic stem/progenitor cell
  • Liver regeneration
  • Mature hepatocyte

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Fujino, H., Hiramatsu, H., Tsuchiya, A., Niwa, A., Noma, H., Shiota, M., Umeda, K., Yoshimoto, M., Ito, M., Heike, T., & Nakahata, T. (2007). Human cord blood CD34+ cells develop into hepatocytes in the livers of NOD/SCID/γcnull mice through cell fusion. FASEB Journal, 21(13), 3499-3510. https://doi.org/10.1096/fj.06-6109com