Differential anti-inflammatory and anti-fibrotic activity of transplanted mesenchymal vs. hematopoietic stem cells in carbon tetrachloride-induced liver injury in mice

Bone marrow stem cells nullify acquired and non-acquired diseases of liver through multiple strategies including antiinflammation. However, little is known about the in vivo mechanism of immunomodulation by stem cells in mediating liver cirrhosis. Mesenchymal stem cells (MSC) or hematopoietic stem cells (HSC) isolated from bone marrow of male mice were transplanted into female mice with acute liver inflammation. Serum levels of liver proteins and aminotransferase as well as hepatic antioxidant enzymes were estimated. Immunostaining for the expression of tumor necrosis factor alpha (TNF-alpha). interleukin 6 (IL-6), alpha smooth muscle actin (alpha-SMA) and type I collagen proteins was carried out and the expression of these mRNAs was also studied. After post-transplantation, the levels of serum albumin and aminotransferases became normal and the levels of antioxidants were significantly high in the MSC treated mice compared to HSC and control mice. Necrotic cells and invasion of neutrophils were not observed in histological sections of liver of MSC treated mice. Immunostaining showed that IL-6 and TNF-alpha were not expressed in the MSC treated mice when compared to the control and HSC treated mice. alpha-SMA representing activated myofibroblasts and type I collagen were not expressed in MSC treated group. These inflammatory and fibrogenic results were further confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The acute inflammation ended with the formation of fibrosis in the HSC and control groups by the uncontrolled immunoreactions. Protection mechanism of MSC therapy against injury and fibrosis in the liver occurs by the suppression of inflammation. Our findings suggest that bone marrow MSC are capable of alleviating the immunoreactions leading to the fibrosis in the liver. (C) 2010 Elsevier B.V. All rights reserved.