title: Angiopoietin-1 gene-modified human mesenchymal stem cells promote angiogenesis and reduce acute pancreatitis in rats.
abstract: Mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy. Angiopoietin-1 (ANGPT1) plays an important role in the regulation of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that ANGPT1 gene-modified MSCs might be a potential therapeutic approach for severe acute pancreatitis (SAP) in rats. Human umbilical cord-derived MSCs with or without transfection with lentiviral vectors containing the ANGPT1 gene were delivered through the tail vein of rats 12 h after induction of SAP. Administration of MSCs alone significantly reduced pancreatic injury and inflammation, as reflected by reductions in pancreatitis severity scores and serum amylase and lipase levels as well as reducing the serum levels of proinflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6). Furthermore, administration of ANGPT1-transfected MSCs resulted in not only further reductions in pancreatic injury and serum levels of proinflammatory cytokines, but also promotion of pancreatic angiogenesis. These results suggest that MSCs and ANGPT1 have a synergistic role in the treatment of SAP. ANGPT1 gene-modified MSCs may be developed as a potential novel therapy strategy for the treatment of SAP.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hua
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: He
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Dao-Hai
authors.initials: DH
authors.lastname: Qian
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Lin
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Meng
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Ting-Song
authors.initials: TS
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.
authors.forename: Zhen-Shun
authors.initials: ZS
authors.lastname: Song
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010195:Pancreatitis / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1
keywords: Angiopoietin-1; acute pancreatitis; gene therapy; mesenchymal stem cells