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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells
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Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

机译：糖尿病的细胞替代疗法：从成人肝细胞中生成功能性胰岛素生产组织

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摘要

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immuno-deficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue.
机译：尸体供体的组织可用性不足和终身免疫抑制的需求严重限制了糖尿病患者细胞替代疗法的大规模应用。这项研究表明成人肝脏作为自体β细胞替代疗法的替代组织的潜在用途。通过使用胰腺和十二指肠同源盒基因1（PDX-1）和可溶性因子，我们诱导成人肝细胞向功能性胰岛素产生细胞的全面发展转变。经PDX-1处理的人肝细胞表达胰岛素，将其存储在确定的颗粒中，并以葡萄糖调节的方式分泌激素。当在免疫缺陷的糖尿病小鼠的肾囊下移植时，这些细胞可长时间改善高血糖症。通过允许患者成为他自己的胰岛素产生组织的供体，诱导成年肝脏的发育重定向为糖尿病患者提供了一种细胞替代疗法的潜力。

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