Ductular cell proliferation in islet cell neogenesis induced by incomplete ligation of the pancreatic duct in dogs

Ductular cell proliferation in islet cell neogenesis induced by incomplete ligation of the pancreatic duct in dogs
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DOI:
10.1007/s00595-004-2789-2
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发表时间:
2004-07-01
期刊:
影响因子:
2.5
通讯作者:
Akashi, K
Akashi, K
中科院分区:
医学4区
文献类型:
--
作者:
Nagaya, M;Kubota, S;Akashi, K

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目的.有人认为,胰岛新生可以诱导不完全结扎的胰管在小动物,但是,还没有报道的新生和增殖的胰岛发生在较大的动物。当这个过程中进行的Vervet猴,它产生了显着增加导管增殖,但胰岛新生没有观察到,虽然猴子的数量是非常小的检查。我们进行了这项研究,以评估是否可以诱导胰岛新生和导管增殖在较大的动物,如狗,通过部分梗阻胰管。用2-0丝线将胰管绕头腹侧结扎,缩小80%左右,造成胰管部分梗阻,造成胰管不完全结扎。结扎后2周,我们看到上皮细胞增生,立方细胞多层,导管细胞增殖。终末小管参与化学胰岛素阳性胰岛的形成,胰岛形成于小管细胞排列附近。结扎后8周,我们看到分散的胰岛,直径小于50 μ m,面积小于1000 μ m(2)。这些细胞被胰岛素和细胞角蛋白免疫标记,并且这些胰岛素阳性细胞和末端导管细胞之间存在连续性。胰高血糖素阳性细胞和生长抑素阳性细胞也被发现毗邻导管细胞排列。这些结果表明,胰岛可能是从胰腺导管中的前体细胞分化而来的,并且干细胞甚至存在于成人中。
Purpose. It has been suggested that islet neogenesis can be induced by incomplete ligation of the pancreatic duct in small animals; however, there has been no report of neogenesis and the proliferation of islets occurring in larger animals. When this procedure was performed in the Vervet monkey, it produced a noticeable increase in duct proliferation, but islet neogenesis was not observed, although the number of monkeys examined was very small. We conducted this study to evaluate whether islet neogenesis and ductular proliferation could be induced in larger animals such as the dog, by partial obstruction of the pancreatic duct.Methods. Incomplete ligation of the pancreatic duct was induced by tying the pancreas around the ventral side of the head with 2-0 silk and reducing the circumference by about 80% to cause partial obstruction.Results. By 2 weeks after ligation, we saw hyperplasia of the epithelial cells, multilayering of cuboidal cells, and proliferation of ductular cells. The terminal ductules involved in the formation of immunohistochemically insulin-positive islets, and islets, formed adjacent to the alignment of the ductular cells. By 8 weeks after ligation we saw scattered islets, less than 50 mum in diameter and less than 1 000 mum(2) in area. These cells were immunolabeled for both insulin and cytokeratin, and there was continuity between these insulin-positive cells and terminal ductular cells. Glucagon-positive cells and somatostatin-positive cells were also found adjacent to the alignment of ductular cells.Conclusions. These results suggest that islets may be differentiated from precursor cells in the pancreatic duct, and that stem cells exist even in adults.