Transplanted Human Cord Blood Cells Give Rise to Hepatocytes in Engrafted Mice

Abstract

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.

Correction of factor IX deficiency in mice by embryonic stem cells differentiated in vitro

“…These fusion events, however, have been in engraftment that involves individual cells in the liver parenchyma, rather than the diffuse engraftment of hundreds of contiguous cells in islands as seen in our model. Furthermore, pluripotent fractions of umbilical cord blood can engraft into the liver with low rates of fusion (25,26) Although fusion as a primary mechanism of the large-scale engraftment seen in our model is excluded, more detailed future studies are required to see whether a low rate of fusion could be present.…”

Embryonic Mouse STO Cell–Derived Xenografts Express Hepatocytic Functions in the Livers of Nonimmunosuppressed Adult Rats

“…In addition, there are conflicting reports on the significance of fusion in normal replacement of liver cells. For example, two recent reports suggest that human cord blood mononuclear cells give rise to human hepatocytes in recipient immune-deficient nonobese diabetic/severe combined immunodeficiency mice, with no evidence of fusion [56,57]; whereas using Cre-lox donor recipient models, both positive [58] and negative [59] fusion results have been obtained. Further experiments are needed to support our tentative conclusion.…”

Activation of interleukin-6-induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration

“…Although the therapeutic effect of stem cell transplantation is promising, previous studies have suggested that less than 1% of transplanted MSCs are constituted to the total organ mass. 25,26 The fate of stem cells after transplantation remains an important issue. In our study, we also encountered the same problem.…”