Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats With Acute and Chronic Pancreatitis

被引:41
作者
Kawakubo, Kazumichi [1 ]
Ohnishi, Shunsuke [1 ]
Fujita, Hirotoshi [2 ]
Kuwatani, Masaki [1 ]
Onishi, Reizo [1 ]
Masamune, Atsushi [3 ]
Takeda, Hiroshi [2 ]
Sakamoto, Naoya [1 ]
机构
[1] Hokkaido Univ, Fac Pharmaceut Sci, Grad Sch Med, Dept Gastroenterol & Hepatol, N15,W7, Sapporo, Hokkaido 0608638, Japan
[2] Hokkaido Univ, Fac Pharmaceut Sci, Lab Pathophysiol & Therapeut, N15,W7, Sapporo, Hokkaido 0608638, Japan
[3] Tohoku Univ, Grad Sch Med, Div Gastroenterol, Sendai, Miyagi 980, Japan
基金
日本学术振兴会;
关键词
mesenchymal stem cells; acute pancreatitis; chronic pancreatitis; macrophages; fetal membrane; amnion; BONE-MARROW; NECROTIZING PANCREATITIS; STELLATE CELLS; MODEL; IDENTIFICATION; EXPRESSION; FIBROSIS; DEATH;
D O I
10.1097/MPA.0000000000000541
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objectives: 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-a 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.
引用
收藏
页码:707 / 713
页数:7
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