A novel antifibrotic strategy utilizing conditioned media obtained from miR-150-transfected adipose-derived stem cells: validation of an animal model of liver fibrosis

The limitations of stem cells have led researchers to investigate the secretome, which is the secretory materials in stem cells, since the principal mechanism of action of stem cells is mediated by the secretome. In this study, we determined the antifibrotic potential of the secretome released from miR-150-transfected adipose-derived stromal cells (ASCs). The secretome released from ASCs that were transfected with antifibrotic miR-150 was obtained (referred to as the miR-150 secretome). To validate the antifibrotic effects of the miR-150 secretome, we generated in vitro and in vivo models of liver fibrosis by treating human hepatic stellate cells (LX2 cells) with thioacetamide (TAA) and subcutaneous injection of TAA into mice, respectively. In the in vitro model, more significant reductions in the expression of fibrosis-related markers, such as TGF beta, Col1A1, and alpha-SMA, were observed by using the miR-150 secretome than the control secretome, specifically in TAA-treated LX2 cells. In the in vivo model, infusion of the miR-150 secretome into mice with liver fibrosis abrogated the increase in serum levels of systemic inflammatory cytokines, such as IL-6 and TNF-alpha, and induced increased expression of antifibrotic, proliferation, and antioxidant activity markers in the liver. Our in vitro and in vivo experiments indicate that the miR-150 secretome is superior to the naive secretome in terms of ameliorating liver fibrosis, minimizing systemic inflammatory responses, and promoting antioxidant enzyme expression. Therefore, we conclude that miR-150 transfection into ASCs has the potential to induce the release of secretory materials with enhanced antifibrotic, proliferative, and antioxidant properties. Regenerative medicine: Training stem cells to fix liver fibrosis A mixture of molecules produced by genetically modified stem cells could help repair the damage associated with liver fibrosis. Fat-derived adipose stem cells (ASCs) secrete proteins and nucleic acids that can facilitate tissue regeneration, but the natural mixture of molecules secreted (the 'secretome') is insufficient to reverse advanced fibrosis. Researchers led by Say-June Kim of the Catholic University of Korea, Seoul, South Korea, have boosted the potency of this cell-derived treatment by engineering ASCs to produce an RNA called miR-150. This RNA inhibits biological processes that drive fibrosis. Experiments in cultured cells and a mouse model of fibrosis confirmed that miR-150 consistently improved the ASC secretome's capacity to control liver fibrosis and minimize systemic inflammatory responses. This approach could thus offer a safe strategy for promoting tissue regeneration and preventing liver failure.