Tissue Engineering and Regenerative Medicine

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver disease and broadly defined by the presence of steatosis with inflammation and progressive fibrosis. Recently, we have reported the therapeutic potential of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) in liver fibrosis using CCl4-induce chronic mice model. These findings led us to plan next study, whose aim was to assess the effectiveness of ADMPCs in improving NAFLD. ADMPCs were isolated from inguinal adipose tissues of C57 BL/6 mice and expanded. NAFLD model was induced by a single subcutaneous injection of 200 μg STZ two days-after birth followed by feeding a high fat diet beginning at four weeks of age. After randomization of animals, the NAFLD mice received ADMPCs or placebo control via tail vein injection at an age of six weeks and were applied for histological and blood examination at an age of nine weeks. NAFLD model mice with ADMPCs injection exhibited a significant reduction in liver fibrosis and inflammation areas, as evidenced by sirius red staining. Moreover, blood examination showed that plasma adiponectin levels in ADMPCs-treated NAFLD model mice were higher than those in placebo controls. In vitro production of anti-inflammatory cytokines, fibrinolytic enzymes and hepato-protective cytokines examined by ELISA were higher than those of BM-MSCs, suggesting the mode of action of ADMPCs. These results showed the mode of action and proof of concept of systemic injection of ADMPCs in NAFLD, which is a promising therapeutic intervention for the treatment

of patients with NAFLD.