Mesenchymal Stem Cells Improve Glycometabolism and Liver Regeneration in the Treatment of Post-hepatectomy Liver Failure

Abstract

Background The mortality rate of post-hepatectomy liver failure (PHLF) remains very high, and liver transplantation is the only effective treatment regimen for PHLF. Cell transplantation is a potential treatment for liver diseases. Previous studies have proved that mesenchymal stem cells (MSCs) have immunomodulatory functions. In the present study, we found that MSCs promoted glycogen synthesis and liver regeneration in the treatment of PHLF. MSC transplantation also improved the survival rate of rats after 90% partial hepatectomy (PH). In our current study, we aimed to determine the efficacy and mechanism of MSC transplantation in the treatment of PHLF. Methods Mesenchymal stem cells were isolated from Sprague-Dawley rats and cultured using a standardized protocol. The MSCs were transplanted to treat acute liver failure induced by 90% PH. The therapeutic efficacy of MSCs on PHLF was verified through measuring alanine transaminase (ALT), aspartate aminotransferase (AST), international normalized ratio (INR), serum ammonia, liver weight to body weight ratio, blood glucose, and histology. To further study the mechanism of MSC transplantation in treatment for PHLF, we assessed the changes in the AKT/glycogen synthase kinase-3β (GSK-3β)/β-catenin pathway. A-674563 (AKT inhibitor) and SB216763 (GSK-3β inhibitor) were employed to validate our findings. SPSS version 19.0 was used for statistical analysis, and the independent-samples t -test was carried out to analyze the collected data. Results Mesenchymal stem cell transplantation attenuated the liver injury in acute liver failure induced by 90% PH. MSC transplantation improved the glucose metabolism and survival rate in the PHLF model. The effect of MSC transplantation on hepatocyte proliferation might be related to AKT/GSK-3β/β-catenin pathway. Conclusion Mesenchymal stem cell transplantation could be use as a potential treatment for PHLF.

Mesenchymal Stem Cell Transplantation in Newly Diagnosed Type-1 Diabetes Patients: A Phase I/II Randomized Placebo Controlled Clinical Trial

“…Interestingly, we observed that the MSC transplantation could significantly reduce the number of hypoglycemic events in recipients as a major life-threatening complication of T1D in children. This effect was reported in a preclinical study of MSC transplantation for posthepatectomy liver failure (61). Additionally, for the first time, we showed that early transplantation of MSCs significantly reduced the rate of grade II hypoglycemic events in T1D patients compared to late transplantation of MSCs.…”

Mesenchymal stem cells ameliorate lipid metabolism through reducing mitochondrial damage of hepatocytes in the treatment of post-hepatectomy liver failure

“…A PHLF model was established by 90% hepatectomy in rats. This is a classic animal model to simulate PHLF based on the previous studies 19 . The levels of liver enzymes (ALT and AST) in hepatectomized rats were sharply increased.…”

Mesenchymal stromal cells promote liver regeneration through regulation of immune cells

“…Preoperative resveratrol administration enhanced the homing capacity of MSCs into liver tissue, thus decreasing the expression of TNF-α and IL-6 and improving liver regeneration in PH-treated rats [57]. In a 90% PH model, MSCs were proven to improve the glucose metabolism and survival rate of rats with PH-induced ALF via promotion of hepatocyte proliferation through the AKT/GSK-3β/β-catenin pathway [58]. Moreover, implantation of bioencapsulated MSCs promoted liver regeneration and increased the survival rate of 90% PH-treated rats from 21% to 91% via induction of hepatogenic differentiation and the secretion of growth factors [59].…”