The evolution from hepatitis to cirrhosis and end-stage liver failure is a trilogy of developmental process which is difficult to control in clinical treatment. Liver transplantation and cell therapy is considered as a promising solution to end-stage liver failure treatment, which can effectively improve the quality of life and prolong the life of patients. However, liver donor and seeding cell shortage is an obstacle to the above two techniques. In order to solve the problem, researchers are trying to explore more effective treatment methods, such as immunotherapy, stem cell therapy and artificial liver support. Induced hepatic differentiation of stem cells and the development of cell transplantation technology provide a potential prospect for liver replacement therapy.
MSC is one of the important members in the stem cell family. MSCs exist in almost all tissues and which can be isolated and successfully amplified in vitro from bone marrow, adipose tissue, umbilical cord, placenta, fetal liver, muscle tissue and lung tissue [9, 10]. MSCs are a kind of cells with regenerative, secretory and immunomodulatory functions, which have the characteristics of self-replication, multidirectional differentiation potential, hematopoietic support and promotion of stem cell implantation, immune regulation. MSCs have the potential for cellular therapy and have been shown to be beneficial for the a variety of diseases . Human umbilical cord mesenchymal stem cells (hUC-MSCs) have the following characteristics, self-renewal, replicate, low immunogenicity and multi-directional differentiation potential. hUC-MSCs have been extensively studied in protective effect, immune regulation, disease prevention and disease treatment[13–15]. In recent years, hUC-MSCs have become an ideal source of cells for cell therapy and tissue engineering research.
miRNAs are involved in the regulation of multiple genes in embryonic development, such as differentiation, proliferation, and organ formation. In addition, in almost all types of diseases, miRNAs expression levels are significantly different from those in normal tissues[18, 19]. Changes in miRNAs network are closely related to liver diseases, including steatohepatitis, viral hepatitis, liver fibrosis, cirrhosis and hepatocellular carcinoma[24, 25]. miRNAs play an important role in improving the efficiency of liver differentiation. miR122 is the most common and highly abundant miRNA in adult liver. miR122 has been shown to be an important host factor and antiviral target for hepatitis c virus infection. Lou et al. found that MSCs modified with miR122 were more conducive to the treatment of liver fibrosis. Reconstruction of miR122 expression is a promising therapeutic strategy in liver tumor diseases that simultaneously reduces tumor invasiveness and disease recurrence. Another miRNA associated with liver disease is miR185. In the study of Zhou et al., miR185 inhibits the activation of hepatic stellate cells by inhibiting the Ras homolog enriched in brain (RHEB) and rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR) pathways, thus preventing the occurrence of liver fibrosis. miR185 has been found to be involved in the differentiation of myelogenic inhibitory cells. Inhibition of miR185 can promotes adipogenic differentiation and osteogenic differentiation, but no study has been conducted on hepatic differentiation.
The purpose of this study is to explore the effect of miR122 and miR185 overexpression on the hepatic inducing differentiation of hUC-MSCs.