Overexpression of c-Met in bone marrow mesenchymal stem cells improves their effectiveness in homing and repair of acute liver failureReportar como inadecuado




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Stem Cell Research and Therapy

, 8:162

First Online: 05 July 2017Received: 16 March 2017Revised: 13 June 2017Accepted: 19 June 2017

Abstract

BackgroundTransplantation of bone marrow-derived mesenchymal stem cells BMSCs has emerged as a novel therapy for acute liver failure ALF. However, the homing efficiency of BMSCs to the injured liver sites appears to be poor. In this study, we aimed to determine if overexpression of c-Met in BMSCs could promote the homing ability of BMSCs to rat livers affected by ALF.

MethodsOverexpression of c-Met in BMSCs c-Met-BMSCs was attained by transfection of naive BMSCs with the lenti-c-Met-GFP. The impact of transplanted c-Met-BMSCs on both homing and repair of ALF was evaluated and compared with lenti-GFP empty vector transfected BMSCs control BMSCs.

ResultsAfter cells were transfected with the lenti-c-Met-GFP vector, the BMSCs displayed very high expression of c-Met protein as demonstrated by Western blot. In addition, in vitro transwell migration assays showed that the migration ability of c-Met-BMSCs was significantly increased in comparison with that of control BMSCs P < 0.05, and was dependent on hepatocyte growth factor HGF. Furthermore, rats with ALF that received transplanted c-Met-BMSCs showed significantly improved homing ability to the injured liver; this was accompanied by elevated survival rates and liver function in the ALF rats. Parallel pathological examination further confirmed that transplantation of c-Met-BMSCs ameliorated liver injury with reduced hepatic activity index HAI scores, and that the effects of c-Met-BMSCs were more profound than those of control BMSCs.

ConclusionsOverexpression of c-Met promotes the homing of BMSCs to injured hepatic sites in a rat model of ALF, thereby improving the efficacy of BMSC therapy for ALF repair.

Keywordsc-Met Bone marrow mesenchymal stem cells Liver injury Acute liver failure Lentiviral vector AbbreviationsALFAcute liver failure

ALTAlanine transaminase

ASCAdipose tissue-derived mesenchymal stem cell

ASTAspartate aminotransferase

bFGFBasic fibroblast growth factor

BMSCBone marrow-derived mesenchymal stem cell

d-GalNd-Galactosamine

DIRDeep red fluorescence

DMEMDulbecco’s modified Eagle’s medium

ECLEnhanced chemiluminescence

ELISAEnzyme-linked immunosorbent assay

FBSFetal bovine serum

HAIHepatic activity index

HEHematoxylin-eosin

HGFHepatocyte growth factor

HIVHuman immunodeficiency virus

HRPHorseradish peroxidase

HSCHematopoietic stem cell

LPCLiver progenitor cell

LPSLipopolysaccharide

LTLiver transplantation

MSCMesenchymal stem cell

NSNormal saline

PETPolyethylene terephthalate

SDStandard deviation

SDS-PAGESodium dodecyl sulfate-polyacrylamide gel electrophoresis

TBilTotal bilirubin

Tet-OnTetracycline-on

WBWestern blot

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Autor: Kun Wang - Yuwen Li - Tiantian Zhu - Yongting Zhang - Wenting Li - Wenyu Lin - Jun Li - Chuanlong Zhu

Fuente: https://link.springer.com/







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