title: Implanted adipose-derived stem cells attenuate small-for-size liver graft injury by secretion of VEGF in rats.
abstract: Graft injury after small-for-size liver transplantation impairs graft function and threatens the survival of the recipients. The use of adipose-derived stem cells (ADSCs) for liver injury protection and repair is promising. Our aim was to investigate the role of vascular endothelial growth factor (VEGF) secreted by ADSCs in the treatment of small-for-size liver graft injury. Studies were performed using ADSCs with VEGF secretion blocked by RNA interference. In vitro, ADSCs prevented apoptosis of freshly isolated liver sinusoidal endothelial cells (LSECs) by secretion of VEGF. Syngeneic 35% orthotopic liver transplantation followed by implantation of syngeneic ADSCs through the portal vein system was performed using Wistar rats. We found VEGF secreted by implanted ADSCs improved graft microcirculatory disturbances, serum liver function parameters and survival. The improved microcirculatory status was also reflected by reduced hepatocellular damage, especially LSEC apoptosis and improved liver regeneration. These effects were accompanied by decreased expression of endothelin receptor type A, increased Bcl-2/Bax ratio, decreased expression of Bad and elevated proportion of phosphorylated Bad. In conclusion, implanted syngeneic ADSCs attenuated small-for-size liver graft injuries and subsequently enhanced liver regeneration in a rat 35% liver transplantation model. The VEGF secreted by implanted ADSCs played a crucial role in this process.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Multi-Organ Transplantation of Ministry of Public Health, Hangzhou, China.
authors.forename: T
authors.initials: T
authors.lastname: Ma
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Xia
authors.forename: X
authors.initials: X
authors.lastname: Bai
authors.forename: L
authors.initials: L
authors.lastname: Liang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Liang
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D005434:Flow Cytometry; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D007124:Immunoenzyme Techniques; D008102:Liver Circulation; D008107:Liver Diseases / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D008111:Liver Function Tests; D008115:Liver Regeneration; D016031:Liver Transplantation; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat