Commitment of bone marrow cells to hepatic stellate cells in mouse.
OBJECTIVE
Recently, several cells found within the liver have been reported to derive from bone marrow (BM). This study sought to examine the commitment of BM cells to hepatic stellate cell (HSC) lineage in mouse liver.


METHODS
We transplanted BM cells from green fluorescent protein (GFP) transgenic mice into age-matched C57BL/J mice. Hepatic nonparenchymal cells were isolated from the livers of BM-transplanted mice using density gradient centrifugation with Nycodenz. The expression of lineage markers by the isolated cells was evaluated by RT-PCR and immunostaining. We then examined the histology of liver tissues obtained from BM-transplanted mice with and without carbon tetrachloride-induced injury.


RESULTS
GFP-expressing cells with intracytoplasmic lipid droplets comprised 33.4 +/- 2.3% of the cells isolated by density gradient centrifugation. These cells expressed the HSC lineage markers, such as desmin and glial fibrillary acidic protein (GFAP), by both RT-PCR and immunostaining. During a 7-day culture, GFP-positive cells began to express alpha-smooth muscle actin, a marker of activated HSC. In the liver of BM-transplanted mice, GFP-positive nonparenchymal cells expressed GFAP and extended their process around hepatocytes. Upon liver injury, these cells also co-expressed desmin and alpha-smooth muscle actin.


CONCLUSIONS
Nonparenchymal cells, derived from transplanted BM, acquired HSC characteristics in both quiescent and activated states.
Baba
Shinji
S
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto City 606-8507, Japan. barbee@kuhp.kyoto-u.ac.jp
Fujii
Hideaki
H
Hirose
Tetsuro
T
Yasuchika
Kentaro
K
Azuma
Hisaya
H
Hoppo
Toshitaka
T
Naito
Masato
M
Machimoto
Takafumi
T
Ikai
Iwao
I
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002251:Carbon Tetrachloride; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology*; D008107:Liver Diseases / Q000473:pathology* / Q000503:physiopathology; D008115:Liver Regeneration / Q000502:physiology; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D002251:Carbon Tetrachloride