Bone marrow mesenchymal stem cells and liver fibrosis Currently, research on the treatment of liver cirrhosis has been in constant exploration, and cell transplantation has received much attention for its advantages of being widely available, less invasive and repeatable. Due to the powerful proliferative and differentiation potential of stem cells, attempts have been made to apply stem cells for the treatment of various diseases including liver diseases, especially cirrhosis and liver failure. BMSCs have plastic, lateral or cross-lineage differentiation properties and are capable of differentiating into a variety of important functional cells of the body such as neuronal cells/cardiomyocytes/vascular endothelial cells/islet cells/liver cells. MSCs are readily obtained from adult bone marrow and other tissues (e.g., adipose tissue, cord blood), can be expanded in vitro in large numbers, and possess hepatocyte functions. It has been demonstrated that BMSCs can reverse CCL4-induced liver fibrosis by differentiating into hepatocytes; however, it has also been found that BMSCs are also a source of HSCs and myofibroblasts in liver fibrosis. This suggests that BMSCs can differentiate into both hepatocyte-like cells and possibly myofibroblast-like cells, promoting the formation of cirrhosis. The discrepancy in the results of these studies may be due to the different effects of the liver microenvironment on the induction of BMSCs differentiation, therefore, it is a critical question whether the application of BMSCs in the treatment of cirrhosis can reverse liver fibrosis or promote its development. In Russo et al.’s study, BMSCs were differentiated into HSCs and myofibroblasts by applying a lethal dose of radioactivity followed by whole bone marrow transplantation. However, there is a clinical need to observe the effect of BMSCs directly in patients with cirrhosis, so a rat cirrhosis model was established in this experiment. After 4 weeks of administration of BMSCs to the model group, it was found that BMSCs did not significantly improve the liver function of the rats with cirrhosis but, on the contrary, led to the deterioration of liver function; the pathomorphological observation showed that the degree of fibrosis in the BMSCs transplanted group was not significantly better than that in the model group, and the BMSCs transplanted group formed wider fibrous cords. The expression of ColⅠ and GFAP in the BMSCs transplantation group was higher than that in the model group and normal group, which further indicated that BMSCs aggravated the formation of liver fibrosis. In vivo animal studies demonstrated that BMSCs in fibrotic livers could aggravate the progression of liver fibrosis. The regulatory role of TGFβ in the formation and progression of liver fibrosis has been widely accepted, and TGFβ is secreted by a wide range of sources, including HSCs, Kupffer cells, endothelial cells, and hepatocytes. TGFβ activates Smad2/3 in the cytoplasm by binding to the serine/threonine kinase-containing TGFβ type II and type I receptors on the cell surface, causing phosphorylation and binding to Smad4 to form a complex that is transferred to the nucleus, where it binds to gene sequences as a transcription factor and causes the expression of related genes. Smad3 is one of the most important members of the TGFβ/Smad signaling pathway. In this experiment, we found that the expression of TGFβ1 and Smad3 was upregulated in the transplanted BMSCs, indicating that the transplanted BMSCs promoted the high expression of TGFβ/Smad signaling pathway, and the high expression of TGFβ1 signaling in turn promoted more cell activation, such as the activation of HSCs into myofibroblast-like cells, which secreted more extracellular matrix and promoted the progression of liver fibrosis. This experiment proved that the treatment effect of transplantation of BMSCs alone is poor, but a large number of studies have shown that BMSCs induced by Hepatocyte growth factor (HGF) in vitro can differentiate into hepatocytes, secrete albumin, improve liver function and reverse liver fibrosis, which provides a better idea for researchers. With further research, the role of BMSCs in different stages of liver disease development