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从人胰腺外分泌细胞体外生成胰岛素分泌细胞。

In vitro generation of insulin-secreting cells from human pancreatic exocrine cells.

机构信息

Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology ; Laboratory for Somatic Stem Cell Therapy, Foundation for Biomedical Research and Innovation, Kobe.

Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University, Kyoto.

出版信息

J Diabetes Investig. 2011 Aug 2;2(4):271-5. doi: 10.1111/j.2040-1124.2010.00095.x.

DOI:10.1111/j.2040-1124.2010.00095.x
PMID:24843497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4014966/
Abstract

Transplantation of surrogate β-cells is a promising option for the treatment of insulin-deficient diabetes mellitus in the future. Although pancreatic exocrine cells of rodents have been shown to transdifferentiate into insulin-secreting cells, no studies are reported on human exocrine cells. Here, we report the generation of insulin-secreting cells from exocrine cells of the human pancreas. When cultured in suspension with epidermal growth factor, human pancreatic exocrine cells readily formed spherical cell clusters. Expression of Pdx1 was induced in all 19 cases in which we successfully isolated exocrine cells, and insulin expression was induced in 11 cases. In addition, insulin secretion was evaluated in four cases, and the newly-made cells were found to secrete insulin in response to various stimuli. Although further studies are required to improve both the quality and quantity of such insulin-secreting cells, our data suggest that pancreatic exocrine cells represent a potential source of insulin-secreting cells for treatment of type 1 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00095.x, 2011).

摘要

胰岛细胞移植是未来治疗胰岛素缺乏型糖尿病的一种很有前途的选择。虽然啮齿动物的胰腺外分泌细胞已被证明可以转分化为胰岛素分泌细胞,但尚未有关于人外分泌细胞的研究报道。在此,我们报告了从人胰腺外分泌细胞中产生胰岛素分泌细胞的方法。当用人表皮生长因子在悬浮培养中培养时,人胰腺外分泌细胞很容易形成球形细胞簇。我们成功分离出外分泌细胞的 19 例中,所有的 Pdx1 表达均被诱导,11 例中诱导了胰岛素表达。此外,我们对 4 例进行了胰岛素分泌的评估,发现新生成的细胞可以响应各种刺激分泌胰岛素。虽然需要进一步研究来提高这些胰岛素分泌细胞的质量和数量,但我们的数据表明,胰腺外分泌细胞可能是治疗 1 型糖尿病的胰岛素分泌细胞的潜在来源。(J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00095.x, 2011)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e97c/4014966/02f8d2b54b2a/jdi-2-271-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e97c/4014966/f4c699614f3b/jdi-2-271-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e97c/4014966/14919e384825/jdi-2-271-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e97c/4014966/02f8d2b54b2a/jdi-2-271-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e97c/4014966/f4c699614f3b/jdi-2-271-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e97c/4014966/14919e384825/jdi-2-271-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e97c/4014966/02f8d2b54b2a/jdi-2-271-g3.jpg

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本文引用的文献

1
Genes controlling pancreas ontogeny.控制胰腺个体发育的基因。
Int J Dev Biol. 2008;52(7):823-35. doi: 10.1387/ijdb.072444cb.
2
In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.成年胰腺外分泌细胞在体内重编程为β细胞。
Nature. 2008 Oct 2;455(7213):627-32. doi: 10.1038/nature07314. Epub 2008 Aug 27.
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Pancreatic acinar-to-beta cell transdifferentiation in vitro.体外胰腺腺泡细胞向β细胞的转分化
Front Biosci. 2008 May 1;13:5824-37. doi: 10.2741/3119.
4
Role of cadherin-mediated cell-cell adhesion in pancreatic exocrine-to-endocrine transdifferentiation.钙黏蛋白介导的细胞间黏附在胰腺外分泌细胞向内分泌细胞转分化中的作用
J Biol Chem. 2008 May 16;283(20):13753-61. doi: 10.1074/jbc.M710034200. Epub 2008 Mar 10.
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Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells.从人胚胎干细胞中产生表达胰腺激素的内分泌细胞。
Nat Biotechnol. 2006 Nov;24(11):1392-401. doi: 10.1038/nbt1259. Epub 2006 Oct 19.
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International trial of the Edmonton protocol for islet transplantation.胰岛移植埃德蒙顿方案的国际试验。
N Engl J Med. 2006 Sep 28;355(13):1318-30. doi: 10.1056/NEJMoa061267.
7
Generation of insulin-secreting cells from pancreatic acinar cells of animal models of type 1 diabetes.从1型糖尿病动物模型的胰腺腺泡细胞中生成胰岛素分泌细胞。
Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E158-65. doi: 10.1152/ajpendo.00180.2006. Epub 2006 Aug 22.
8
Expansion and redifferentiation of adult human pancreatic islet cells.成人人类胰岛细胞的扩增与再分化
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Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells.成体胰腺腺泡细胞来源的胰岛素分泌细胞的谱系追踪与特性分析
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10
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Diabetologia. 2005 Jan;48(1):49-57. doi: 10.1007/s00125-004-1606-1. Epub 2004 Dec 23.