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Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-05-1338. This Article Full Text (PDF) All Versions of this Article: 2002-05-1338v1 101/10/4201    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 Wang, X. Articles by Nolta, J. A Search for Related Content PubMed PubMed Citation Articles by Wang, X. Articles by Nolta, J. A Social Bookmarking                   What's this? Submitted May 8, 2002 Accepted December 23, 2002 Albumin expressing hepatocyte-like cells develop in the livers of immune-deficient mice transmitted with highly purified human hematopoietic stem cells Xiuli Wang, Shundi Ge, George McNamara, Qian-Lin Hao, Gay M Crooks, and Jan A Nolta* Division of Research Immunology/ Bone Marrow Transplantation, Childrens Hospital of Los Angeles, Los Angeles, CA, USA Research Institute, Childrens Hospital of Los Angeles, Los Angeles, CA, USA * Corresponding author; email: jnolta{at}im.wustl.edu. Recent intriguing observations indicate that stem cell plasticity may exist. Rodent bone marrow cells have been shown to contribute to liver. If these findings are applicable to humans, marrow stem cells could theoretically be harvested from a patient and used to repair his/her damaged liver. To explore this potential, CD34+ or highly purified CD34+CD38-CD7- human hematopoietic stem cells from umbilical cord blood and bone marrow were transplanted into immunodeficient mice. One month post-transplantation 0.4ml/kg carbon tetrachloride (CCl4) was administered into the mice to induce massive liver damage and hepatocyte proliferation. Mice were analyzed in comparison to CCl4 injured non-transplanted and non-injured controls transplanted with the same stem cell populations, one month after liver damage. Human-specific albumin mRNA and protein was expressed in the mouse liver, and human albumin was detected in the murine serum, in mice that had received CCl4 injury. Human AFP was never expressed in the livers of any of the mice, but in some mice human cytokeratin 19 was expressed, which may indicate bile duct development in addition to the albumin secreting hepatocyte-like cells. Human albumin was not expressed in the starting stem cell populations, in injured, non-transplanted mice or in non-injured mice that had been transplanted with human stem cells. Human albumin expression was only detected in human stem cell transplanted, CCl4-treated mice, and recovery was increased by administration of human hepatocyte growth factor (HGF) 48 hours after the CCl4-mediated liver injury. Our studies provide evidence that human "hematopoietic" stem/progenitor cell populations have the capacity to respond to the injured liver microenvironment by inducing albumin expression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Yadav, S. Kanjirakkuzhiyil, S. Kumar, M. Jain, A. Halder, R. Saxena, and A. Mukhopadhyay The therapeutic effect of bone marrow-derived liver cells in the phenotypic correction of murine hemophilia A Blood, November 12, 2009; 114(20): 4552 - 4561. 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