Bone mesenchymal stem cell transplantation via four routes for the treatment of acute liver failure in rats

Abstract

In the present study, we assessed the efficiency of four BMSC transplantation methods as a therapy for liver failure. A rat model (80 Sprague-Dawley rats) of D-galactosamine (D-gal)/lipopolysaccharide (LPS)-induced acute liver failure (ALF) was established and the rats were divided into 5 groups: a hepatic artery injection group, a portal vein injection group, a vena caudalis injection group, an intraperitoneal injection group and a control group (16 per group). Following transplantation, the liver tissue and blood samples were collected on days 1, 3 and 7, we detected the EdU (5-ethynyl-2′-deoxyuridine)-labeled cells homing to the liver tissue and assessed the proliferating cell nuclear antigen (PCNA) and cysteine-containing aspartate-specific protease (caspase)-3 expression in the liver tissue and detected the levels of stromal cell-derived factor 1 (SDF-1) and hepatocyte growth factor (HGF) in the liver tissues. Compared with the control group, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and damage to the liver tissue in the hepatic artery group, the portal vein group and the vena caudalis group improved in vivo. The expression of PCNA and HGF in the liver was higher and caspase-3 expression was lower in the hepatic artery injection group, the portal vein injection group and the vena caudalis injection group than that in the intraperitoneal injection and control groups. The EdU-labeled BMSCs were only observed homing to the liver tissue in these three groups. However, no significant differences were observed between these three groups. Liver function in the rats with ALF was improved following BMSC transplantation via 3 endovascular implantation methods (through the hepatic artery, portal vein and vena caudalis). These 3 methods were effective in transplanting BMSCs for the treatment of ALF. However, the selection of blood vessel in the implantation pathway does not affect the transplantation outcome. Transplantation via intraperitoneal injection showed no therapeutic effect in our animal experiments.

Effect of Yi Guan Jian decoction on differentiation of bone marrow mesenchymalstem cells into hepatocyte-like cells in dimethylnitrosamine-induced liver cirrhosis in mice

“…The chemokine stromal cell-derived factor-1 (SDF-1) binds to CXCR4. Numerous studies have reported that SDF-1 is critical for stem/progenitor and mesenchymal cell chemotaxis and inflammatory cell homing to injured tissue via interaction with CXCR4 on the surface of these cells; CXCR4 maybe highly expressed in humans and mice following chemotaxis along an SDF-1 gradient (24,25). This indicates that the level of CXCR4 expression may reflect the activation of the SDF-1/CXCR4 axis, which is associated with stem cells.…”

Transplantation of umbilical cord blood-derived mesenchymal stem cells to treat liver cirrhosis in mice: a comparison of tail and portal vein injection

“…Similar to our study, recent studies in rats have also found that MSC infusion via portal vein is more beneficial than caudal vein with regards to MSC "homing" and improvement of liver function . In a study by Sun et al (2014) which compared four different routes of bone marrow (BM)-MSC transplantation in a rat model, portal vein administration was found to have greater impact on stem cell "homing" than the other routes (Sun et al, 2014). Furthermore, portal vein was the best route for transplanting MSCs and improved rat liver function compared to hepatic artery, peripheral vein or intrahepatic routes (Sang et al, 2016).…”

Treatment Efficiency of Different Routes of Bone Marrow-Derived Mesenchymal Stem Cell Injection in Rat Liver Fibrosis Model

“…Moreover, the relationship between transplantation route and transplantation efficacy is unclear [15]. In the present study, we injected BM-MSCs through two different routes (intravenous and intrasplenic) and compared their efficacy for the management of CCl 4 -induced liver fibrosis and also assessed the conceivable mechanisms underlying this effect.…”