Autophagy-Modulated Human Bone Marrow-Derived Mesenchymal Stem Cells Accelerate Liver Restoration in Mouse Models of Acute Liver Failure.
Iran Biomed J
; 20(3): 135-44, 2016 07.
Article
in En
| MEDLINE
| ID: mdl-26899739
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
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.CONCLUSION:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Liver Failure, Acute
/
Mesenchymal Stem Cell Transplantation
/
Mesenchymal Stem Cells
/
Cell- and Tissue-Based Therapy
/
Liver Regeneration
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Iran Biomed J
Journal subject:
BIOLOGIA
/
MEDICINA
Year:
2016
Document type:
Article
Affiliation country:
Iran
Publication country:
IR
/
IRAN
/
IRÃ