title: Autophagy-Modulated Human Bone Marrow-Derived Mesenchymal Stem Cells Accelerate Liver Restoration in Mouse Models of Acute Liver Failure.
abstract: Mesenchymal stem cells (MSCs) have been recently received increasing attention for cell-based therapy, especially in regenerative medicine. However, the low survival rate of these cells restricts their therapeutic applications. It is hypothesized that autophagy might play an important role in cellular homeostasis and survival. This study aims to investigate the regenerative potentials of autophagy-modulated MSCs for the treatment of acute liver failure (ALF) in mice.
  
  
  
  ALF was induced in mice by intraperitoneal injection of 1.5 ml/kg carbon tetrachloride. Mice were intravenously infused with MSCs, which were suppressed in their autophagy pathway. Blood and liver samples were collected at different intervals (24, 48 and 72 h) after the transplantation of MSCs. Both the liver enzymes and tissue necrosis levels were evaluated using biochemical and histopathological assessments. The survival rate of the transplanted mice was also recorded during one week.
  
  
  
  Biochemical and pathological results indicated that 1.5 ml/kg carbon tetrachloride induces ALF in mice. A significant reduction of liver enzymes and necrosis score were observed in autophagy-modulated MSC-transplanted mice compared to sham (with no cell therapy) after 24 h. After 72 h, liver enzymes reached their normal levels in mice transplanted with autophagy-suppressed MSCs. Interestingly, normal histology without necrosis was also observed.
  
  
  
  Autophagy suppression in MSCs ameliorates their liver regeneration potentials due to paracrine effects and might be suggested as a new strategy for the improvement of cell therapy in ALF.
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Amiri
authors.affiliation: School of Medicine, Qom University of Medical Sciences, Qom, Iran.
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Molaei
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Marzie
authors.initials: M
authors.lastname: Bahadori
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Nasiri
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Deyhim
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Jalili
authors.affiliation: Research Center of Molecular Biology, Baqiyatallah Medical Sciences University, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Nourani
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Mehryar
authors.initials: M
authors.lastname: Habibi Roudkenar
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071193:Autophagy-Related Protein 7 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D017114:Liver Failure, Acute / Q000473:pathology / Q000628:therapy*; D008115:Liver Regeneration / Q000502:physiology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice
chemical_list: C502661:Atg7 protein, mouse; D002251:Carbon Tetrachloride; D000071193:Autophagy-Related Protein 7
keywords: Acute liver failure; Autophagy; Mesenchymal stem cells