title: Intravenous hMSCs Ameliorate Acute Pancreatitis in Mice via Secretion of Tumor Necrosis Factor-α Stimulated Gene/Protein 6.
abstract: The administration of mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) to enhance tissue repair is currently undergoing clinical trials. Some studies, including our previous work, have also revealed the beneficial effect of MSCs in severe acute pancreatitis (SAP); however, their mechanisms or mode of action remain controversial. In this study, we demonstrated that intravenously (i.v.)-administered human MSCs (hMSCs) remarkably promoted recovery from experimental SAP without significant engraftment of hMSCs in the damaged pancreas. Interestingly, we found that i.v.-administered hMSCs with knockdown of TSG-6 expression lost most of their anti-inflammatory effects and thus could not significantly ameliorate SAP. As expected, the effects of hMSCs were also duplicated by i.v. infusion of recombinant TSG-6. Furthermore, our results showed that the increase of oxidative stress, activation of the NLRP3 inflammasome and NF-κB signaling in SAP was substantially inhibited following administration of hMSCs or TSG-6, which was dependent on the presence of CD-44 receptors in acinar cells. In conclusion, our study, for the first time, revealed that novel mechanisms are responsible for the immunomodulatory effect of i.v. hMSCs.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hua
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Daohai
authors.initials: D
authors.lastname: Qian
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Shengping
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Chenglei
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Tingsong
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Zhenshun
authors.initials: Z
authors.lastname: Song
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology; D056747:Immunomodulation / Q000235:genetics*; D058847:Inflammasomes / Q000008:administration & dosage / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D016328:NF-kappa B / Q000235:genetics; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D010195:Pancreatitis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C476399:Cd44 protein, mouse; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D058847:Inflammasomes; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C513057:Tnfaip6 protein, mouse; D014409:Tumor Necrosis Factor-alpha