Human cord blood cells transplanted into chronically damaged liver exhibit similar characteristics to functional hepatocytes.
Human umbilical cord blood (CB) cells have many advantages as a source for stem cell transplantation because of immaturity and availability. It has been reported that CB cells transplanted into an injured liver displayed hepatocyte-like phenotypes. However, there have been few studies to characterize CB-derived hepatocyte-like cells (HLCs). In this study, CB cells were transplanted into mice with 2 types of liver damage: transient and chronic damage. We analyzed the expression of hepatic differentiation markers in CB-derived HLCs. In the liver of NOD/SCID mice with transient damage, CB-derived HLCs were detected infrequently at 3 weeks after transplantation. In contrast, in the liver of SCID mice damaged chronically by a urokinase-type plasminogen activator transgene under the control of albumin promotor/enhancer (ALB-uPA/SCID mice), more human HLCs colonized the host liver compared with hosts with transiently damaged livers. The CB-derived HLCs in both the transiently and the chronically damaged liver expressed a few markers of human hepatocytes, whereas the transcripts related to mature hepatic functions, including cytochrome P450s, were detected only in the ALB-uPA/SCID mice. These data indicated that CB cells were able to display a similar phenotype to functional hepatocytes in the recipient liver with chronic damage. CB cells may represent a transplantable source for chronic decompensated liver disease.
Kakinuma
S
S
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan. kakinuma@ims.u-tokyo.ac.jp
Asahina
K
K
Okamura
K
K
Teramoto
K
K
Tateno
C
C
Yoshizato
K
K
Tanaka
Y
Y
Yasumizu
T
T
Sakamoto
N
N
Watanabe
M
M
Teraoka
H
H
D000818:Animals; D036101:Cord Blood Stem Cell Transplantation; D022781:Hepatocytes / Q000473:pathology* / Q000502:physiology; D006801:Humans; D008099:Liver / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous