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Bone Marrow Cell Transplant Does Not Prevent or Reverse Murine Liver Cirrhosis

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Abstract:

We tested the effect of bone marrow cell (BMC) transplantation in either preventing or reversing cirrhosis on an experimental model of chronic liver disease. Female Wistar rats were fed a liquid alcohol diet and received intraperitoneal injections of carbon tetrachloride (CCl4) over 15 weeks. Ten animals (cell-treated group) received five injections of BMCs during the cirrhosis induction protocol (on the 4th, 6th, 8th, 10th, and 12th weeks) and four animals received the cells after liver injury was established through tail vein. Nine animals (nontreated group) were submitted to the previously described protocols; however, they received vehicle injections. Analyses were performed to verify whether the infusion of cells was effective in preventing the development of cirrhosis in our model of induction, and if the cells could reverse cirrhosis once it was established. Hepatic architecture and fibrotic septa were analyzed in liver slices stained with hematoxilin & eosin and Sirius red, respectively. Fibrosis quantification was measured by Sirius red histomorphometry. Indirect immunofluorescence was performed to detect the amount of tissue transglutaminase 2. Blood analyses were performed to assess liver injury and function by the assessment of alanine aminotransferase and albumin. Ultrasound was performed to analyze the portal vein caliber and presence of ascitis. Cirrhosis features (regenerative nodules and fibrous septa) were observed in histopathology after 15 weeks of continuous hepatic injury in nontreated and cell-treated groups. Collagen content, immunofluorescence analysis, and biochemical and ultrasound parameters were similar in nontreated and cell-treated groups; however, both groups showed significant differences compared to a normal control group. Cell infusions with bone marrow-derived cells seem to be ineffective in improving morphofunctional parameters of the liver when applied to chronic cases either during or after establishment of the hepatic lesion.

Keywords: Biochemistry; Bone marrow cell; Cirrhosis; Histology; Ultrasound

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368908786576453

Publication date: August 1, 2008

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.

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