title: Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats With Acute and Chronic Pancreatitis.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine and can be isolated from fetal membranes (FMs), particularly amniotic membranes. We investigated the effect of rat FM-derived MSCs (rFM-MSCs) and human amnion-derived MSCs (hAMSCs) on the inflammatory reaction in vitro and therapeutic effects in rats with acute and chronic pancreatitis.
  
  
  METHODS
  Effect of rFM-MSCs or hAMSC-conditioned medium was investigated in vitro. Acute pancreatitis was induced by intraductal injection of 4% taurocholate, and rFM-MSCs were transplanted intravenously. Chronic pancreatitis was induced by intravenous injection of 5 mg/kg dibutyltin dichloride, and hAMSCs were transplanted intravenously.
  
  
  RESULTS
  The inflammatory reaction of macrophages induced by lipopolysaccharide and trypsin was significantly suppressed by rFM-MSC coculture. Pancreatic acinar cell injury induced by cerulein was significantly ameliorated by hAMSC-conditioned medium. Pancreatic stellate cell activation induced by tumor necrosis factor-α was significantly decreased by hAMSC-conditioned medium. Transplantation of rFM-MSCs significantly reduced the histological score and infiltration of CD68-positive macrophages in the rat pancreas. The hAMSC transplantation significantly decreased the expression of MCP-1 and attenuated the downregulation of amylase expression in the pancreas.
  
  
  CONCLUSIONS
  Transplantation of FM-MSCs and AMSCs suppressed the inflammatory reaction of acute and chronic pancreatitis in rats.
authors.affiliation: From the *Department of Gastroenterology and Hepatology, Graduate School of Medicine, †Laboratory of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; and ‡Division of Gastroenterology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Kawakubo
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Masaki
authors.initials: M
authors.lastname: Kuwatani
authors.forename: Reizo
authors.initials: R
authors.lastname: Onishi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masamune
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
mesh_terms: D061354:Acinar Cells / Q000187:drug effects / Q000473:pathology; D000208:Acute Disease; D000681:Amylases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005321:Extraembryonic Membranes / Q000166:cytology*; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D058954:Pancreatic Stellate Cells / Q000187:drug effects; D010195:Pancreatitis / Q000628:therapy*; D050500:Pancreatitis, Chronic / Q000628:therapy*; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000681:Amylases