Supplementary MaterialsSupplementary Components: Identification of human umbilical cord-mesenchymal stem cells (hUCMSCs). in vitroexperiments, MSCs were treated in serum-free culture for 72 h to simulate the disruption of intrahepatic microcirculation. MSCs apoptosis was examined to determine whether ICT rescued impaired MSCs. The role of the hepatocyte growth factor (HGF)/c-Met pathway in MSCs was assessed by constructing genetically modified MSCs overexpressing c-Met and by using the c-Met receptor inhibitor (crizotinib). The results showed that MSCs increased the survival rate of ALF rats and reduced liver damage. MSCs cocultured with ICT exerted a greater therapeutic effect than MSCs alone. Further, the HGF/c-Met pathway played a key role in the antiapoptotic activity of MSCs, which was associated with the optimized efficacy of ICT. In conclusion, this study exhibited that ICT enhances the therapeutic effect of MSCs in a model of ALF, improving the antiapoptotic potential of MSCs by upregulation of the HGF/c-Met pathway. The combination of stem cell therapy with traditional herbal extracts may improve MSC-based clinical applications. 1. Introduction Acute liver failure (ALF) is usually BET-IN-1 a severe, rapidly deteriorating disease characterized by the abrupt onset of severe liver injury and high mortality. Liver transplantation is one of the most effective treatment for ALF; however, the shortage of donor organizations remains a major obstacle to its application. Hence, substitute remedies are required urgently. Lately, mesenchymal stem cells (MSCs) show excellent prospect of many healing applications. A lot of studies predicated on stem cell transplantation possess achieved remarkable outcomes and provided brand-new ways for the treating various illnesses. For ALF, MSCs certainly are a guaranteeing treatment because they possess the to differentiate into hepatocytes to revive liver organ function and offer immune legislation to suppress inflammatory storms [1]. Many reports [2] show that MSCs transfusion is certainly safe and simple for liver organ failure; it could improve liver function and ascites in experimental animal and patients [3]. However, the efficacy of MSCs is limited by their poor survival rate and their inability to adapt to extreme pathological environments [4]. Therefore, researchers must increase the number of stem cell infusions and the frequency of infusion BET-IN-1 therapy, which greatly affects the efficacy and, on the other hand, increases the cost BET-IN-1 of treatment Goat polyclonal to IgG (H+L) and reduces treatment compliance, making it difficult to popularize. Therefore, there is an urgent need for strategies to improve the efficacy of stem cell therapies. Many therapeutic strategies have been devised to improve stem cell adaptability to unfavorable environments. Silk Fibroin Complex Matrices have functioned as ideal scaffold for MSCs [5]. A nanoparticle was fabricated and coated with red blood cell membranes that increased blood stability and carried useful factors from MSCs [6]. A combination of MSCs and nanoparticles, loaded with IL-lRa, was investigated BET-IN-1 [7]. In recent studies, reprogrammed pluripotent cell-specific factors (CXCR4 and Oct4) were used to construct gene-modified MSCs to promote colonization of MSCs [8C12], but the use of new materials such as nanoparticles or scaffolds is limited because of their high cost. Moreover, the carcinogenic risk of gene modification technology remains controversial. Soluble cytokine growth factors, such as platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF), have been reported to promote the proliferation of MSCs, although the mechanism is usually unclear. Their use is limited because they are cost prohibitive and place cells in a state of stress [13]. Therefore, attention has turned to natural herbs and their vast milieu of phytochemicals as replacements for synthetic formulations [14]. As alternative therapeutics, natural products such as purified compounds from traditional herbal extracts have exceptional characteristics: low toxicity, affordability, and availability [13]. Research examined the systems and ramifications of organic ingredients in the natural activity of MSCs, including proliferation, differentiation, apoptosis, autophagy, and senescence [13, 15C17]. Icaritin (ICT) is certainly a hydrolytic item of icariin produced from the genusEpimedium98%; Sigma, St. Louis, MO, USA); galactosamine (D-GalN; Sigma); lipopolysaccharide (LPS; Sigma); individual HGF BET-IN-1 (ReproTech, Columbia, Missouri, USA); crizotinib (MedChemExpress, Monmouth.