title: 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.
authors.affiliation: The Endocrine Institute, The Institute for Pathology, and The Maurice and Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Sapir
authors.forename: Keren
authors.initials: K
authors.lastname: Shternhall
authors.forename: Irit
authors.initials: I
authors.lastname: Meivar-Levy
authors.forename: Tamar
authors.initials: T
authors.lastname: Blumenfeld
authors.forename: Hamutal
authors.initials: H
authors.lastname: Cohen
authors.forename: Ehud
authors.initials: E
authors.lastname: Skutelsky
authors.forename: Smadar
authors.initials: S
authors.lastname: Eventov-Friedman
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.forename: Iris
authors.initials: I
authors.lastname: Goldberg
authors.forename: Sarah
authors.initials: S
authors.lastname: Pri-Chen
authors.forename: Lya
authors.initials: L
authors.lastname: Ben-Dor
authors.forename: Sylvie
authors.initials: S
authors.lastname: Polak-Charcon
authors.forename: Avraham
authors.initials: A
authors.lastname: Karasik
authors.forename: Ilan
authors.initials: I
authors.lastname: Shimon
authors.forename: Eytan
authors.initials: E
authors.lastname: Mor
authors.forename: Sarah
authors.initials: S
authors.lastname: Ferber
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation / Q000648:ultrastructure; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008854:Microscopy, Electron; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose