Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration.
Ischemia-reperfusion (I/R) associated with small-for-size liver transplantation (SFSLT) impairs liver graft regeneration. Mesenchymal stem cells (MSCs) have the capability, under specific conditions, of differentiating into hepatocytes. Hepatocyte growth factor (HGF) has potent anti-apoptotic and mitogenic effects on hepatocytes during liver injury, and has been utilized in many experimental and clinical applications. In this study, we implanted HGF-expressing MSCs into liver grafts via the portal vein, using a 30% small-for-size rat liver transplantation model. HGF, c-met expression, hepatic injury and liver regeneration were assessed after liver transplantation. Our study demonstrated that MSCs over-expressing HGF prevented liver failure and reduced mortality in rats after SFSLT. These animals also exhibited improved liver function and liver weight recovery during the early post-transplantation period. Using green fluorescent protein (GFP) gene as a marker, we demonstrated that the engrafted cells and their progeny incorporated into remnant livers and produced albumin. These findings suggest that MSCs genetically modified to over-express HGF and implanted in the liver graft, may offer a novel approach to promoting liver regeneration after small-for-size transplantations.
Yu
Yue
Y
The Liver Transplantation Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Yao
Ai-Hua
AH
Chen
Nian
N
Pu
Li-Yong
LY
Fan
Ye
Y
Lv
Ling
L
Sun
Bei-Cheng
BC
Li
Guo-Qiang
GQ
Wang
Xue-Hao
XH
D000818:Animals; D017209:Apoptosis; D002469:Cell Separation; D002470:Cell Survival; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008115:Liver Regeneration; D016031:Liver Transplantation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009929:Organ Size; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015996:Survival Rate; D019076:Transgenes / Q000235:genetics; D015854:Up-Regulation
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met