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Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-05-1338.
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.
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