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

Dig Dis Sci. 2010 Dec;55(12):3384-92. doi: 10.1007/s10620-010-1195-4. Epub 2010 Apr 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / analysis
  • Animals
  • Bone Marrow Transplantation*
  • Carbon Tetrachloride / adverse effects
  • Cell Proliferation
  • Cell Tracking / methods
  • Chemical and Drug Induced Liver Injury / surgery*
  • Culture Media, Conditioned
  • Female
  • Hepatocytes / physiology*
  • Leukocytes, Mononuclear / transplantation*
  • Male
  • Mitosis / physiology
  • Rats
  • Rats, Wistar

Substances

  • Culture Media, Conditioned
  • Carbon Tetrachloride
  • Alanine Transaminase