Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells
| Autor: | Tamar Blumenfeld, Lya Ben-Dor, Sarah Ferber, Avraham Karasik, Keren Shternhall, Iris Goldberg, Smadar Eventov-Friedman, Eytan Mor, Irit Meivar-Levy, Ilan Shimon, Hamutal Cohen, Tamar Sapir, Ehud Skutelsky, Iris Barshack, Sarah Pri-Chen, Sylvie Polak-Charcon |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Cellular differentiation Carbohydrate metabolism Biology Islets of Langerhans Renal capsule Transduction Genetic Diabetes mellitus Internal medicine medicine Humans Homeodomain Proteins Multidisciplinary Insulin Cell Differentiation Immunosuppression Genetic Therapy Biological Sciences medicine.disease Diabetes Mellitus Type 1 medicine.anatomical_structure Endocrinology Hepatocytes Trans-Activators Immunohistochemistry Genetic Engineering Hormone |
| Zdroj: | Proceedings of the National Academy of Sciences. 102:7964-7969 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0405277102 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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