Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells.
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.
Sapir
Tamar
T
The Endocrine Institute, The Institute for Pathology, and The Maurice and Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel-Hashomer 52621, Israel.
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
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
D017931:DNA Primers; D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose