Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice.
OBJECTIVE
We examined whether bone marrow (BM) cells can commit to liver-consisting cells during liver regeneration after partial hepatectomy, using mice transplanted with green fluorescent protein (GFP) positive BM from GFP transgenic mice.


METHODS
Partial hepatectomy or sham operation was performed. Lineage marker analysis of GFP positive liver cells was by immunostaining and flow cytometry. DiI-labeled acetylated low-density lipoprotein uptake or microsphere phagocytosis was examined in vitro. Lineage marker expression in BM and peripheral blood (PB) cells, and the vascular endothelial growth factor (VEGF) concentration in the liver were also examined.


RESULTS
In hepatectomized mice, significantly more GFP positive cells participated in liver sinusoid than in sham-operated mice, expressing CD31 but not albumin. The percentage of cells that incorporated acetylated low-density lipoprotein but not microspheres was 69.5+/-3.4%, while 28.3+/-2.6% incorporated both, revealing sinusoidal endothelial and Kupffer cells, respectively. Increased expression of the CD31 and CD16/CD32 on GFP positive liver cells was also detected. The elevation of the VEGF concentration during liver regeneration and the increase in the CD34 and Flk-1 expression in the liver, BM, and PB cells suggested endothelial progenitor cell mobilization.


CONCLUSIONS
GFP cell-marking provided direct evidence of the BM cells participation in liver regeneration after hepatectomy, where the majority was committed to sinusoidal endothelial cells probably through endothelial progenitor cell mobilization.
Fujii
Hideaki
H
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, 54, Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. hideaki@kuhp.kyoto-u.ac.jp
Hirose
Tetsuro
T
Oe
Shoshiro
S
Yasuchika
Kentaro
K
Azuma
Hisaya
H
Fujikawa
Takahisa
T
Nagao
Masaya
M
Yamaoka
Yoshio
Y
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000737:chemistry / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000502:physiology; D016228:Endothelial Growth Factors / Q000032:analysis; D005434:Flow Cytometry; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006498:Hepatectomy; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007202:Indicators and Reagents / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics; D008099:Liver / Q000166:cytology*; D008115:Liver Regeneration / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics; D008222:Lymphokines / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010587:Phagocytosis; D013234:Stem Cells / Q000737:chemistry / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000096:biosynthesis; D042442:Vascular Endothelial Growth Factors
D018952:Antigens, CD34; D016228:Endothelial Growth Factors; D007202:Indicators and Reagents; D036341:Intercellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D008164:Luminescent Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C032629:acetyl-LDL; D049452:Green Fluorescent Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2