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

Abstract

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. Stem Cells Translational Medicine 2017;6:272–284

Optimization of lentiviral transduction parameters and its application for CRISPR-based secretome modification of human endometrial mesenchymal stem cells

“…Probably, the underlying cause of the adverse effects of Pb + LV infection on MSCs proliferation rate observed previously by other authors might also be cell senescence [23]. Of note, in the modern studies, Pb is actively used to increase the effectiveness of MSCs transduction for either purpose, what with regard to our results may somehow distort the data obtained by the authors [57][58][59][60].…”

“…Additionally, Flt-1-engineered MSCs caused regression of endometriotic lesions [50]. A plenty of other fascinating results are obtained by applying MSCs with genetically modified paracrine activity [57,58,63,64]. However, in the vast majority of studies, the gain-of-function genetic perturbations are obtained by the use of cDNA overexpression systems.…”

Clinical Study of Mesenchymal Stem Cell Treatment for Acute Respiratory Distress Syndrome Induced by Epidemic Influenza A (H7N9) Infection: A Hint for COVID-19 Treatment

“…The viability ranged from 90%−95%. Additionally, the surface makers and three-line differentiation of MSCs are conducted and the detail information is referenced as previous study [37,38].…”

Strategies to improve the efficiency of mesenchymal stem cell transplantation for reversal of liver fibrosis

“…14 In contrast, menstrual blood-derived stem cells were demonstrated to eliminate collagen deposition and inhibit proliferative HSCs via paracrine mediators, but few of the transplanted cells differentiated into functional hepatocyte-like cells despite migrating to the sites of injury. 15 Transplanted MSCs up-regulate the expression levels of key enzymes associated with glucose metabolism in carbon tetrachloride (CCl 4 )-induced liver cirrhotic rats, thus maintaining normal metabolic status in liver fibrotic rats. 16 (SKP2) level, attenuating the ubiquitination of p27 and increasing the stability of p27.…”