The Role of Bone Marrow Mesenchymal Stem Cells in the Treatment of Acute Liver Failure

Abstract

Objective. This study is to investigate the effects of bone marrow mesenchymal stem cell (BMSC) transplantation on acute liver failure (ALF). Methods. BMSCs were separated from rat bone marrow, cultured, and identified by flow cytometry. Rat model with ALF was established by injecting D-galactosamine and lipopolysaccharide. Rats were randomly divided into the control group and BMSC transplantation group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at 24 h, 120 h, and 168 h after BMSC transplantation. Apoptosis was detected by TUNEL assay. The expression of VEGF and AFP proteins was detected by immunofluorescence. Caspase-1 and IL-18 proteins and mRNA were detected by immunohistochemistry and RT-PCR. Results. Compared with the control group, levels of ALT, AST, caspase-1 and IL-18 proteins, and mRNA in the transplantation group were significantly lower at 120 h and 168 h after BMSCs transplantation. Apoptosis was inhibited by BMSCs transplantation. The VEGF protein levels were increased with the improvement of liver function, and the AFP protein levels were increased with the deterioration of the liver function after BMSCs transplantation. Conclusions. BMSCs transplantation can improve liver function and inhibit hepatocyte apoptosis as well as promote hepatocyte proliferation in rat model with ALF.

Extracellular Vesicles from Bone Marrow-Derived Mesenchymal Stem Cells Improve Survival from Lethal Hepatic Failure in Mice

“…In mice, there is a lower expression of Y-RNA-1 in the liver, compared to other organs. MSC have been reported to have anti-apoptotic effects on hepatocytes [4][5][6][7] in vivo. During experimental renal injury induced by cisplatin, MSCderived microvesicles were shown to modulate the expression of several different anti-apoptotic genes or effectors of apoptosis within human tubular epithelial cells [9].…”

Bone marrow-derived mesenchymal stem cells attenuate acute liver injury and regulate the expression of fibrinogen-like-protein 1 and signal transducer and activator of transcription 3

“…Recently, studies have demonstrated that BMSCs reinforce liver regeneration and have significant suppressive effects on hepatocyte apoptosis (36)(37)(38). BMSCs suppress proapoptotic protein expression and enhance anti-apoptotic protein expression, consequently attenuating hepatocyte degeneration and subsequent apoptosis, as well as accelerating hepatocyte regeneration (39).…”

Downregulation of microRNA‐214 improves therapeutic potential of allogeneic bone marrow–derived mesenchymal stem cell by targeting PIM‐1 in rats with acute liver failure

“…With a high mortality rate, early recognition and transfer to a medical care center with transplant facilities is critical and essential for ALF patients . Multiple treatments for ALF, including drug therapy, artificial liver therapy, stem cell transplantation, and liver transplantation are in current medical use for patients suffering with ALF . Additionally, there is a survival rate of approximately 75% of patients who undergo emergency liver transplantation .…”