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‡,**, and
- Sarah Ferber*,‡,††
- *The Endocrine Institute, ¶The Institute for Pathology, and ∥The Maurice and Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel-Hashomer 52621, Israel; †Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel; ‡Sackler School of Medicine, Tel Aviv University, Ramat-Aviv 69978, Israel; §Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel; **Rabin Medical Center, Beilinson Campus, Petah-Tiqva 49100, Israel
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Edited by C. Ronald Kahn, Harvard Medical School, Boston, MA, and approved April 8, 2005 (received for review July 22, 2004)
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.
Footnotes
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↵ †† To whom correspondence should be addressed at the * address. E-mail: sferber{at}sheba.health.gov.il.
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This paper was submitted directly (Track II) to the PNAS office.
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Abbreviations: PDX-1, pancreatic and duodenal homeobox gene 1; AHL, adult human liver; TAHL, transdifferentiated AHL; SFs, soluble factors; moi, multiplicity of infection; NOD-SCID, nonobese diabetic severe combined immunodeficient.
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See Commentary on page 7781.
- Copyright © 2005, The National Academy of Sciences
