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Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells.


ABSTRACT: 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, immunodeficient 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.

SUBMITTER: Sapir T 

PROVIDER: S-EPMC1142350 | biostudies-literature | 2005 May

REPOSITORIES: biostudies-literature

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Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells.

Sapir Tamar T   Shternhall Keren K   Meivar-Levy Irit I   Blumenfeld Tamar T   Cohen Hamutal H   Skutelsky Ehud E   Eventov-Friedman Smadar S   Barshack Iris I   Goldberg Iris I   Pri-Chen Sarah S   Ben-Dor Lya L   Polak-Charcon Sylvie S   Karasik Avraham A   Shimon Ilan I   Mor Eytan E   Ferber Sarah S  

Proceedings of the National Academy of Sciences of the United States of America 20050517 22


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-produ  ...[more]

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