Mesenchymal stem cell (MSC) transplantation is a novel treatment for liver diseases due to the roles of MSCs in regeneration, fibrosis inhibition and immune regulation. However, the mechanisms are still not completely understood. Despite the significant efficacy of MSC therapy in animal models and preliminary clinical trials, issues remain. The efficacy and safety of MSC-based therapy in the treatment of liver diseases remains a challenging issue that requires more investigation. This article reviews recent studies on the mechanisms of MSCs in liver diseases and the associated challenges and suggests potential future applications.
After Friedenstein et al. (1) first isolated and identified stromal cells from bone marrow in 1966, mesenchymal stem cells (MSCs) were isolated from various tissues, such as the umbilical cord (2, 3), placenta (4), adipose tissue (5, 6), amniotic fluid (7, 8), menstrual blood (9, 10), and dental pulp (11). The immunomodulatory properties, limited self-renewal capacity, and multi-lineage development of MSCs make these cells ideal candidates for clinical applications in different diseases (12). The low inherent immunogenicity of MSCs guarantees transplant safety (13). Even HLA-mismatched MSCs could be used for many clinical applications, especially for stem cell-based therapies (14). Moreover, the ability of these cells to home to specific organs and lesions is the key to the curative effect of MSC transplantation (13). MSC surface chemokine receptors, such as CCR1, CCR4, CCR7, CXCR5, and CCR10, are involved in the migration of MSCs into injured tissues along chemokine gradients (15). MSCs are administered to patients by various routes, such as intravascular injection and local transplantation, to alleviate diseases (16–18).
Liver diseases are a global health issue that cause a large number of deaths every year (19, 20). Liver transplantation, which is recommended as the only effective treatment method available for advanced liver diseases, is limited by high costs and a shortage of donor livers (21). MSC transplantation brings new hope to the treatment of liver diseases. Despite their different etiologies, symptoms and physiological processes, multiple kinds of life-threating liver diseases can be effectively treated by cell-based therapy, as three decades of clinical and preclinical studies proved. Among the most used source of cells for allogenic/autologous transplantation, the two most largely clinically infused cells are undoubtedly primary hepatocyte and MSCs. MSCs have been administered in hundreds of clinical trials during the past decades, and for a plethora of indications (Table 1). Although many laboratory and clinical trials have confirmed the efficacy of MSCs in a variety of diseases, there are still no guidelines to regulate MSC clinical applications (29–31).