Enhancement of mesenchymal stem cells liver regeneration potentialities in acute liver failure by authophagy suppression

Introduction: Acute liver failure (ALF) is liver tissue injury with extensive necrosis and associated with high rates of morbidity. Mesenchymal stem cells (MSCs) are suitable cells for cell-based therapy especially in regenerative medicine. However, their therapeutic potentials might be limited due to low survival. Autophagy plays an important role in cellular homeostasis and survival. In this study, we assay the regenerative potentials of autophagy-modulated-MSCs for the treatment of ALF in mice model. Materials and methods: Carbon tetrachloride was utilized for induction of ALF in mice. MSCs which are suppressed in their autophagy pathway were transplanted into ALF-induced-mice as well as normal MSCs. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as liver enzymes, and tissue necrosis levels were evaluated using biochemical and pathological methods. Results: ALT and AST level dropped significantly in the mice which received autophagy-modulated-MSCs in comparison with sham group (with no cell therapy) after 24 hrs. Necrosis score was also decreased in the test group. Liver enzymes retained their normal levels in mice transplanted with autophagy-suppressed MSCs during 72 hrs post transplantation and normal histology without necrosis was also observed. Conclusion: Suppression of autophagy in mesenchymal stem cells prompted liver regeneration potential more likely due to paracrine effects. It might be suggested as a new strategy for the improvement of cell therapy inacute liver failure

کلیدواژه ها:

Acute liver failure ، Mesenchymal stem cells ، Autophagy ، Cell therapy