Liver fibrosis is a necessary stage in the evolution of various chronic liver diseases into cirrhosis, and because of the excessive deposition of extracellular matrix (ECM) and the relative reduction of functional hepatocytes, replacing the lost hepatocytes has become a hot topic of research in recent years. Currently, liver transplantation is considered an effective clinical treatment for replacing non-functional hepatocytes, but its application is limited by the lack of donor, surgical injury, rejection and high price. Cell transplantation, on the other hand, has the advantages of being widely available, less invasive and repeatable, and bone marrow stem cell (BMSC) is considered to be the most promising donor cell. However, the most suitable for BMSC treatment may be those types of liver parenchymal cell defects with more complete liver fiber scaffold, such as acute liver failure, genetic metabolic liver disease, etc. Liver fibrosis has different etiology, course and pathology from other types of liver disease, and the application of BMSC transplantation has its own special characteristics, and views are different, which need to be understood and considered comprehensively. 1. Transplantation advantages of BMSC Cell transplantation for clinical application needs to meet the following 3 aspects: ① sufficient cell quantity reserve: ② satisfactory cell transplantation status; ③ smooth proliferation after cell transplantation. The transplanted cells that have been used for clinical treatment of liver fibrosis and cirrhosis or are in the research stage so far include mature hepatocytes, intrahepatic stem cells (such as oval cells), peripheral blood stem cells, BMSC, embryonic stem cells, fetal liver cells and umbilical cord blood cells, etc. However, some of them are not fully feasible as donor cells, for example, mature hepatocytes are difficult to obtain intact and have a short life span in vitro and are prone to rapid loss of function, are larger than the diameter of the hepatic sinusoidal gap, and cannot easily enter the target area. For example, mature hepatocytes are difficult to obtain intact, have a short life span in vitro and are prone to rapid loss of function. Thus, the advantages of BMSC transplantation are that they are easy to collect and can be expanded in vitro in large numbers, can self-renew and differentiate into various cell types, are small in size to facilitate access to the liver parenchyma, are autologous without immune rejection, and do not involve ethical issues. 2. Transplantation sites and routes of BMSC 2.1. Intrahepatic transplantation The effect is direct. The transplantation routes are divided into three types: trans-peripheral vein, portal vein and direct intrahepatic injection. The first two of them are widely used because of their relatively simple operation. However, in addition to the relative reduction of functional hepatocytes, liver fibrosis also has excessive deposition of ECM, which can lead to the destruction of liver tissue structure, narrowing of the hepatic sinusoidal gap, obstruction of cell entry into the liver parenchyma, or even blockage of the portal vein. Direct intrahepatic injection avoids the requirement of targeting and the obstruction of disordered tissues, but the cells may enter the central vein in addition to colonizing the liver tissue, increasing the risk of pulmonary embolism, so it is only suitable for basic research. 2.2. Intrasplenic transplantation appears to have advantages over intrahepatic transplantation in the treatment of end-stage disease with severe structural destruction of liver tissue. There are two transplantation routes: trans-splenial artery and direct splenic marrow infusion. The former is easily adopted clinically, but may affect cellular implantation and function and may result in splenic infarction due to vascular embolism caused by donor cells. The latter is better tolerated and has better efficacy than splenic artery injection. The only possibility is to cause intra-abdominal hemorrhage and is considered the most feasible route of cell transplantation for the treatment of histologically disordered liver disease, but the adequacy of the number of BMSC implants in the spleen, survival time, differentiation capacity and metabolic function remain to be further explored. 2.3. Peritoneal transplantation Large capacity and easy access. However, since BMSC is in suspension in the abdominal cavity and cannot enter the liver, it may be effective in the short term but cannot survive in the long term and cannot eliminate the cause of the disease, and is rarely used in animal experiments and is even more distant from the clinic. 3, the effect and mechanism of BMSC transplantation for liver fibrosis Although the quantity and quality of BMSC can be maintained after transplantation into the liver is still inconclusive, and the results of some studies seem to contradict theoretically that BMSC transplantation can improve liver fibrosis, many studies on treatment in recent years have still achieved promising results. Animal studies have demonstrated that BMSC transplantation significantly reduces collagen deposition and hydroxyproline content in liver tissue, inhibits transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle alpha-actin (α-SMA) expression, decreased serum pro-collagen type III amino-terminal peptide (PIIIP), hyaluronic acid and laminin levels, and sustained expression and secretion of albumin, thereby reducing the extent of liver fibrosis, improving liver function (e.g., increased serum albumin levels, decreased ghrelin and total bilirubin levels, etc.), improving quality of life (e.g., improved appetite, weight gain, decreased ascites, etc.), and reducing mortality. It is worth noting that liver fibrosis is a progressive process, and once it reaches an irreversible stage or even cirrhosis, is BMSC transplantation still effective?Zhao et al. showed that BMSC transplantation after 10 days of liver fibrosis induction with dimethylnitrosamine was more effective than those performed after 20 days. Others found that BMSC transplantation after 1 week of CTC-induced liver fibrosis had no antifibrotic effect, although intrahepatic implants were seen, thus suggesting that BMSC transplantation should be performed at an early stage of liver fibrosis. However, more studies have shown that BMSC transplantation at the 4th to 6th week of liver fibrosis model still has a good antifibrotic effect. Recently, some scholars in China have used BMSC transplantation via hepatic artery to treat 30 patients with decompensated cirrhosis with satisfactory results, and liver function and clinical symptoms were significantly improved without serious adverse effects or complications [23], which brings hope for the treatment of patients with severe liver fibrosis and cirrhosis. 4. problems and prospects At present, the treatment of liver fibrosis is still a major problem, and BMSC transplantation has brought light to many patients with liver fibrosis and cirrhosis and is considered one of the most promising measures for application, but there are still many problems to be solved. For example, whether there is a dominant subpopulation or a unique subpopulation of BMSC differentiated into hepatocytes, what are the mechanisms of interaction and migration between multiple subpopulations of BMSC, what are the factors influencing the targeted implantation of BMSC in fibrotic liver, and what are the biological properties of BMSC in the hepatic fibrotic environment? What are the microenvironment and mechanisms that determine which cell lineage BMSC differentiate to in the liver? What are the specific mechanisms of action and signaling pathways of BMSC against liver fibrosis? And so on. If some measures can be elucidated and targeted to improve the efficacy and safety of BMSC transplantation in liver fibrosis, it will bring a revolution in the treatment of liver fibrosis.