Recent studies suggest that rodent hepatocytes may be derived from hematopoietic stem cells. In the current study, the potential hematopoietic origin of hepatocytes was addressed using xenogeneic transplantation of human cord blood cells. CD34(+) or CD45(+) human cord blood cells were transplanted into "conditioned" newborn NOD/SCID/beta2-microglobulin(null) mice. At 4 to 5 months post-transplantation, livers of the recipient mice were cryosectioned and examined for evidence of human hepatocyte engraftment using RT-PCR to detect human albumin mRNA, immunohistochemistry to detect human hepatocytic proteins, and fluorescence in situ hybridization (FISH) to detect the presence of human centromeric DNA. Analysis of the bone marrow of transplanted mice revealed that 21.0-45.9% of the cells were human CD45(+) cells. FISH analysis of frozen sections of transplanted mouse liver revealed the presence of engrafted cells positive for human centromeric DNA. That engrafted human cells functioned as hepatocytes was indicated by the expression of human albumin mRNA, as judged by RT-PCR. FISH analysis with human and mouse centromeric DNA probes excluded spontaneous cell fusion as the cause for the generation of human hepatocytes. Human cord blood cells can give rise to hepatocytes in a xenogeneic transplantation model. This model will be useful to further characterize the cord blood progenitors of hepatocytes.

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There have been controversies about CD34 and CD38 expression by human cord blood (CB) stem cells. Using the newborn NOD/SCID/b2-microglobulin-null mouse assay that we recently developed, we examined the in vivo engrafting capability of human CB cells. Almost all of the 4-5 months engrafting cells were found in CD34 + population. The capability of secondary reconstitution was found only in the CD34 + cells. When the CD34 + CB cells were separated into CD38 À and CD38 + subpopulations and tested for engraftment, the majority of the engrafting cells were detected in the CD38 À subpopulation. These findings are consistent with the results from studies of murine stem cells and strongly indicate that the phenotype of human CB stem cells is CD34 + CD38 À . Leukemia (2003) 17, 960-964.

The fetal sheep competitive engraftment model of human hematopoietic stem cells (HSC) was used to evaluate the in vivo engraftment potential of human bone marrow CD34- Lin- cells. Transplantation of CD34- Lin- cells into primary hosts resulted in the long-term (> 1 year) engraftment and multilineage donor cell/progenitor expression with production of significant numbers of CD34+ cells. Secondary transplantation and limiting dilution studies confirmed the presence in human CD34- fraction of HSC with in vivo long-term engraftment and multilineage differentiation potentials.