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

Tamar Sapir, Keren Shternhall, Irit Meivar-Levy, Tamar Blumenfeld, Hamutal Cohen, Ehud Skutelsky, Smadar Eventov-Friedman, Iris Barshack, Iris Goldberg, Sarah Pri-Chen, Lya Ben-Dor, Sylvie Polak-Charcon, Avraham Karasik, Ilan Shimon, Eytan Mor, Sarah Ferber*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

246 Scopus citations


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 hyperglycemic 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.

Original languageEnglish
Pages (from-to)7964-7969
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number22
StatePublished - 31 May 2005


  • Pancreas
  • Transdifferentiation


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