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Abstract
Background: Mesenchymal stem cells transplantation has recently gained widespread enthusiasm particularly in the perspective to use them to treat acute and chronic liver diseases. A stem cell niche is the restricted compartment in a tissue that maintains and regulates stem cell behaviour, supporting self-renewal and maintaining the balance between quiescence, proliferation and differentiation required in response to injury. Accordingly, understanding how the niche influences stem/progenitor cells behaviour is therefore likely to be of scientific and clinical importance if novel strategies are to be developed to promote liver regeneration in the setting of chronic liver injury. Aim of the work: It was intended in this study to determine the behaviour of transplanted stem cells within the liver and to elucidate the interaction of these stem cells with niche cells, soluble factors and the factors that regulate homing of stem cells to the liver during the process of liver injury induced by carbon tetrachloride (CCl4). Materials and Methods: Experimental animal models were designed to identify the behavior of transplanted stem cells in response to liver damage and their relationship to hepatic stem cell niche. Superparamagnetic iron oxide (SPIO) - labeled MSCs were injected into mice in which liver fibrosis by carbon tetrachloride CCl4 was induced. To identify the role of macrophages as one cellular component of the niche, selective hepatic macrophage-depleted animal model subgroup was used using clodronate liposome. Transplanted labeled stem cells are then traced for their homing into their niche and were studied for their differentiation into hepatocytes, neovasculature or myofibroblasts and these activities were correlated with various levels of soluble factors released in the stem cell niche compartment at early and late stages of liver fibrosis