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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2427-2435. Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-07-101261. This Article Full Text (PDF) All Versions of this Article: blood-2007-07-101261v1 111/4/2427    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Miyata, E. Articles by Katayama, N. Search for Related Content PubMed PubMed Citation Articles by Miyata, E. Articles by Katayama, N. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 13, 2007 Accepted November 16, 2007 Hematopoietic origin of hepatic stellate cells in the adult liver Eri Miyata, Masahiro Masuya*, Shuro Yoshida, Shiho Nakamura, Keizo Kato, Yuka Sugimoto, Tetsunori Shibasaki, Kentaro Yamamura, Kohshi Ohishi, Kazuhiro Nishii, Fumihiko Ishikawa, Hiroshi Shiku, and Naoyuki Katayama Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan Blood Transfusion Service, Mie University Hospital, Tsu, Mie, Japan Research Unit for Human Disease Model, RIKEN Center for Allergy and Immunology, Yokohama, Kanagawa, Japan * Corresponding author; email: mmasuya{at}clin.medic.mie-u.ac.jp. Hepatic stellate cells are believed to play a key role in the development of liver fibrosis. Several studies have reported that bone marrow cells can give rise to hepatic stellate cells. We hypothesized that hepatic stellate cells are derived from hematopoietic stem cells. To test this hypothesis, we generated chimeric mice by transplantation of clonal populations of cells derived from single enhanced green fluorescent protein (EGFP)-marked Lin-Sca-1+c-kit+CD34- cells and examined the histology of liver tissues obtained from the chimeric mice with carbon tetrachloride (CCl4)-induced injury. After 12 weeks of CCl4 treatment, we detected EGFP+ cells in the liver and some cells contained intracytoplasmic lipid droplets. Immunofluorescence analysis demonstrated that 50-60% of the EGFP+ cells were negative for CD45 and positive for vimentin, glial fibrillary acidic protein, ADAMTS13, and -smooth muscle actin. Moreover, EGFP+ cells isolated from the liver synthesized collagen I in culture. These phenotypes were consistent with those of hepatic stellate cells. The hematopoietic stem cell-derived hepatic stellate cells seen in male-to-male transplants revealed only one Y chromosome. Our findings suggest that hematopoietic stem cells contribute to the generation of hepatic stellate cells after liver injury and that the process does not involve cell fusion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Laje, D. Shang, W. Cao, M. Niiya, M. Endo, A. Radu, N. DeRogatis, F. Scheiflinger, P. W. Zoltick, A. W. Flake, et al. Correction of murine ADAMTS13 deficiency by hematopoietic progenitor cell-mediated gene therapy Blood, March 5, 2009; 113(10): 2172 - 2180. [Abstract] [Full Text] [PDF]

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