Human Menstrual Blood-Derived Stem Cells Ameliorate Liver Fibrosis in Mice by Targeting Hepatic Stellate Cells via Paracrine Mediators.

: Mesenchymal stem cells (MSCs) may have potential applications in regenerative medicine for the treatment of chronic liver diseases (CLDs). Human menstrual blood is a novel source of MSCs, termed menstrual blood-derived stem cells (MenSCs). Compared with bone marrow MSCs, MenSCs exhibit a higher proliferation rate and they can be obtained through a simple, safe, painless procedure without ethical concerns. Although the therapeutic efficacy of MenSCs has been explored in some diseases, their effects on liver fibrosis are still unclear. In the present study, we investigated the therapeutic effects of MenSC transplantation in a carbon tetrachloride-induced mouse model of liver fibrosis. These results revealed that MenSCs markedly improved liver function, attenuated collagen deposition, and inhibited activated hepatic stellate cells up to 2 weeks after transplantation. Moreover, tracking of green fluorescent protein-expressing MenSCs demonstrated that transplanted cells migrated to the sites of injury, but few differentiated into functional hepatocyte-like cells. Transwell coculturing experiments also showed that MenSCs suppressed proliferation of LX-2 cells (an immortalized hepatic stellate cell line) through secretion of monocyte chemoattractant protein-1, interleukin-6, hepatocyte growth factor, growth-related oncogene, interleukin-8, and osteoprotegerin. Collectively, our results provided preliminary evidence for the antifibrotic capacity of MenSCs in liver fibrosis and suggested that these cells may be an alternative therapeutic approach for the treatment of CLDs.

SIGNIFICANCE: This is the first report that the transplantation of human menstrual blood-derived stem cells (MenSCs) has a therapeutic effect on liver fibrosis in a mouse model. Analysis of α-smooth muscle actin and transforming growth factor-β1 expression found that MenSCs suppressed the activated hepatic stellate cells (HSCs). Furthermore, the indirect coculture with LX-2 cells (activated HSCs) showed that MenSCs targeted HSCs through secretion of paracrine mediators (cytokines), namely, monocyte chemotactic protein-1, interleukin-6, hepatocyte growth factor, growth-related oncogene, interleukin-8, and osteoprotegerin. These findings show that MenSCs could be used as a novel therapeutic option for the treatment of chronic liver diseases.