Bone marrow mononuclear cell transplantation improves survival and induces hepatocyte proliferation in rats after CCl(4) acute liver damage.
OBJECTIVE
The aim of this research was to evaluate the effects of bone marrow mononuclear cell (BMC) transplantation in rats with toxic acute liver damage induced by carbon tetrachloride (CCl(4)).


METHODS
Cells from male Wistar rats were obtained using Ficoll density gradient and 0.2 ml (1 × 10(6) cells) were injected into the portal vein of female rats (n = 15) 24 h after damage. Sham group (n = 15) was performed injecting only vehicle in CCl(4)-treated animals. Survival, liver histology, number of mitosis and apoptosis, and identification of stained donor cells were observed 72 h after damage. ALT levels were measured at 0 h, 24 h, 48 h, and 72 h after injury.


RESULTS
Donor cells could be detected in recipient rats' livers by fluorescence staining and Sry PCR. The treated group revealed a significant improvement in survival rate after 72 h (p = 0.003). There was also a significant increase in the number of mitotic events in treated livers (p = 0.029). This result was confirmed using an in vitro cell proliferation assay in isolated hepatocytes treated with conditioned medium from BMC. ALT was reduced in the treated group after 72 h (p = 0.034).


CONCLUSIONS
Results indicate that BMC transplantation has potential as a new therapeutic option for acute liver disease and suggest that these cells may contribute to hepatic recovery through release of mitotic cytokines.
Baldo
Guilherme
G
Gene Therapy Center, Research Center, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350 Porto Alegre, RS, Brazil. guibaldo@ig.com.br
Giugliani
Roberto
R
Uribe
Carolina
C
Belardinelli
Maria Cristina
MC
Duarte
Marcos Eugênio Soares
ME
Meurer
Luíse
L
da Silveira
Themis Reverbel
TR
Matte
Ursula
U
D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D016026:Bone Marrow Transplantation; D002251:Carbon Tetrachloride / Q000009:adverse effects; D049109:Cell Proliferation; D058948:Cell Tracking / Q000379:methods; D056486:Chemical and Drug Induced Liver Injury / Q000601:surgery*; D017077:Culture Media, Conditioned; D005260:Female; D022781:Hepatocytes / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D008938:Mitosis / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D017077:Culture Media, Conditioned; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase
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