Analyses to clarify rich fractions in hepatic progenitor cells from human umbilical cord blood and cell fusion.
Umbilical cord blood (UCB) is a source of hematopoietic stem cells and other stem cells, and human UCB cells have been reported to contain transplantable hepatic progenitor cells. However, the fractions of UCB cells in which hepatic progenitor cells are rich remain to be clarified. In the present study, first, the fractionated cells by CD34, CD38, and c-kit were transplanted via portal vein of NOD/SCID mice, and albumin mRNA expression was examined in livers at 1 and 3 months posttransplantation. At 1 and 3 months, albumin mRNA expression in CD34+UCB cells-transplanted livers was higher than that in CD34- cells-transplanted livers. Albumin mRNA expression in CD34+CD38+ cells-transplanted livers was higher than that in CD34+CD38- cells-transplanted [corrected] liver at 1 month. However, it was much higher [corrected] in CD34+CD38- cell-transplanted livers at 3 months. Similar expression of albumin mRNA was obtained between CD34+CD38+c-kit+ cells- and CD34+CD38-c-kit- cells-transplanted livers, and between CD34+CD38-c-kit+ cells- and CD34+CD38-c-kit- cells-transplanted livers, respectively. Second, fluorescence in situ hybridization and immunohistochemistry were performed to examine whether UCB cells really transdifferentiated into hepatocytes or they only fused with mouse hepatocytes. In mouse liver sections, of 1.2% cells which had human chromosomes, 0.9% cells were due to cell fusion, whereas 0.3% cells were transdifferentiated into human hepatocytes. These results suggest that CD34+UCB cells are rich fractions in hepatic progenitor cells, and that transdifferentiation from UCB cells into hepatocytes as well as cell fusion simultaneously occur in this situation.
Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Faculty of Medicine, Tottori University, Japan.
Yoshitada
Y
Tanabe
Fumihito
F
Tajima
Yuki
Y
Nakamura
Eriko
E
Shibasaki
Mai
M
Wakejima
Takashi
T
Shimomura
Rie
R
Murai
Yoshiyuki
Y
Murawaki
Koichi
K
Hashiguchi
Takamasa
T
Kanbe
Toshiya
T
Saeki
Miho
M
Ichiba
Yoko
Y
Yoshida
Masahiro
M
Mitsunari
Soichi
S
Yoshida
Jun-Ichiro
J
Miake
Yasutaka
Y
Yamamoto
Naoki
N
Nagata
Tasuku
T
Harada
Akihiro
A
Kurimasa
Ichiro
I
Hisatome
Naoki
N
Terakawa
Yoshikazu
Y
Murawaki
Goshi
G
Shiota
D036541:ADP-ribosyl Cyclase / Q000096:biosynthesis; D051997:ADP-ribosyl Cyclase 1; D000418:Albumins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D002454:Cell Differentiation; D002469:Cell Separation / Q000379:methods*; D017690:Cell Transplantation; D002478:Cells, Cultured; D005312:Fetal Blood / Q000378:metabolism*; D005434:Flow Cytometry; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation; D008562:Membrane Glycoproteins; D051379:Mice; D016513:Mice, SCID; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D014470:Umbilical Cord / Q000378:metabolism*
D000418:Albumins; D015703:Antigens, CD; D018952:Antigens, CD34; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019009:Proto-Oncogene Proteins c-kit; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1