Bone marrow mononuclear cell transplantation improves survival and induces hepatocyte proliferation in rats after CCl(4) acute liver damage

Abstract

Aim: 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.