Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats.
OBJECTIVE
The autologous transplantation of bone marrow cells is a promising treatment for liver disease. Pluripotent bone marrow stem cells can differentiate into hepatocytes, but few reports address the therapeutic effect of transplanting these stem cells into damaged liver in vivo. Here, we transplanted bone marrow-derived mesenchymal cells (BMMCs) to test their effect in liver-injured rats.


METHODS
Rat bone marrow cells were cultivated for 2 weeks in the presence or absence of hepatocyte growth factor (HGF), labeled with a fluorescent marker, and transplanted by injection into CCl(4)-injured rats. Blood samples collected 4 weeks later were analyzed for albumin production and transaminase levels. The amount of fibrosis was determined by histology.


RESULTS
RT-PCR analysis detected alpha-fetoprotein and albumin mRNAs in BMMCs cultured with HGF for 2 weeks. Albumin protein was also produced in the BMMC cultures by a subpopulation of cells. Transplantation of the BMMCs into liver-injured rats restored their serum albumin level and significantly suppressed transaminase activity and liver fibrosis. These effects were not seen when the BMMCs were cultured without HGF.


CONCLUSIONS
The transplantation of BMMCs cultured with HGF effectively treats liver injury in rats. This is a promising technique for autologous transplantation in humans with liver injury.
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871 Japan.
Suguru
S
Oyagi
Motohiro
M
Hirose
Midori
M
Kojima
Makiko
M
Okuyama
Masaya
M
Kawase
Toshikazu
T
Nakamura
Hajime
H
Ohgushi
Kiyohito
K
Yagi
D000418:Albumins / Q000032:analysis / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D017690:Cell Transplantation; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D022781:Hepatocytes / Q000737:chemistry / Q000473:pathology; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology* / Q000628:therapy*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012709:Serum Albumin / Q000032:analysis; D000637:Transaminases / Q000097:blood; D000509:alpha-Fetoproteins / Q000032:analysis / Q000235:genetics
D000418:Albumins; D012333:RNA, Messenger; D012709:Serum Albumin; D000509:alpha-Fetoproteins; D017228:Hepatocyte Growth Factor; D002251:Carbon Tetrachloride; D000637:Transaminases