TY - JOUR
T1 - Cell-replacement therapy for diabetes
T2 - Generating functional insulin-producing tissue from adult human liver cells
AU - Sapir, Tamar
AU - Shternhall, Keren
AU - Meivar-Levy, Irit
AU - Blumenfeld, Tamar
AU - Cohen, Hamutal
AU - Skutelsky, Ehud
AU - Eventov-Friedman, Smadar
AU - Barshack, Iris
AU - Goldberg, Iris
AU - Pri-Chen, Sarah
AU - Ben-Dor, Lya
AU - Polak-Charcon, Sylvie
AU - Karasik, Avraham
AU - Shimon, Ilan
AU - Mor, Eytan
AU - Ferber, Sarah
PY - 2005/5/31
Y1 - 2005/5/31
N2 - 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.
AB - 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.
KW - Pancreas
KW - Transdifferentiation
UR - http://www.scopus.com/inward/record.url?scp=20344394437&partnerID=8YFLogxK
U2 - 10.1073/pnas.0405277102
DO - 10.1073/pnas.0405277102
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AN - SCOPUS:20344394437
SN - 0027-8424
VL - 102
SP - 7964
EP - 7969
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 22
ER -
