Bone Marrow Multipotent Mesenchymal Stromal Cells Do Not Reduce Fibrosis or Improve Function in a Rat Model of Severe Chronic Liver Injury

The objective of our study was to evaluate the therapeutic potential of bone marrow mesenchymal stromal cells (MSC) in a rat model of severe chronic liver injury. Fourteen female Wistar rats were fed exclusively an alcoholic liquid diet and received intraperitoneal injections of carbon tetrachloride...

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Bibliographic Details
Published in:	Stem cells (Dayton, Ohio) Vol. 26; no. 5; pp. 1307 - 1314
Main Authors:	Carvalho, Adriana B., Quintanilha, Luiz Fernando, Dias, Juliana V., Paredes, Bruno D., Mannheimer, Elida G., Carvalho, Felipe G., Asensi, Karina D., Gutfilen, Bianca, Fonseca, Lea Mirian B., Resende, Celia Maria C., Rezende, Guilherme F. M., Takiya, Christina M., de Carvalho, Antonio Carlos Campos, Goldenberg, Regina C. S.
Format:	Journal Article
Language:	English
Published:	Bristol John Wiley & Sons, Ltd 01-05-2008
Subjects:	Animals Biomarkers - metabolism Bone marrow Bone Marrow Cells - cytology Chronic Disease Collagen - metabolism Female Fibrosis Injections Liver Liver Diseases - pathology Liver Diseases - physiopathology Liver Function Tests Mesenchymal stromal cells Mesenchymal Stromal Cells - cytology Multipotent Stem Cells - cytology Organotechnetium Compounds Phenotype Rats Rats, Wistar Stromal Cells - cytology
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Summary:	The objective of our study was to evaluate the therapeutic potential of bone marrow mesenchymal stromal cells (MSC) in a rat model of severe chronic liver injury. Fourteen female Wistar rats were fed exclusively an alcoholic liquid diet and received intraperitoneal injections of carbon tetrachloride every other day during 15 weeks. After this period, eight animals (MSC group) had 1 × 107 cells injected into the portal vein while six animals (placebo group) received vehicle. Blood analysis was performed to evaluate alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin before cell therapy and 1 and 2 months after cell or placebo infusion. Fibrosis was evaluated before and 1 month after cell or placebo injection by liver biopsies. Two months after cell delivery, animals were sacrificed and histological analysis of the livers was performed. Fibrosis was quantified by histomorphometry. Biopsies obtained before cell infusion showed intense collagen deposition and septa interconnecting regenerative nodules. One month after cell injection, this result was unaltered and differences in fibrosis quantification were not found between MSC and placebo groups. ALT and AST returned to normal values 2 weeks after cell or placebo infusion, without significant differences between experimental groups. Two months after cell or placebo injection, albumin had also returned to normal values and histological results were maintained, again without differences between MSC and placebo groups. Therefore, under our experimental conditions, MSC were unable to reduce fibrosis or improve liver function in a rat model of severe chronic liver injury. Disclosure of potential conflicts of interest is found at the end of this article.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1066-5099 1549-4918
DOI:	10.1634/stemcells.2007-0941