https://scholars.lib.ntu.edu.tw/handle/123456789/545685
標題: | PDGF facilitates direct lineage reprogramming of hepatocytes to functional β-like cells induced by Pdx1 and Ngn3 | 作者: | Chang F.-P. Cho C.H.-H. Shen C.-R. Chien C.-Y. Ting L.-W. Lee, Hsuan-Shu Shen C.-N. |
關鍵字: | Glucagon-like peptide-1 (GLP-1); Hepatocyte transdifferentiation; Lineage reprogramming; Platelet-derived growth factor (PDGF); Type 1 diabetes mellitus; β-Cells | 公開日期: | 2016 | 出版社: | Cognizant Communication Corporation | 卷: | 25 | 期: | 10 | 起(迄)頁: | 1893-1909 | 來源出版物: | Cell Transplantation | 摘要: | Islet transplantation has been proven to be an effective treatment for patients with type 1 diabetes, but a lack of islet donors limits the use of transplantation therapies. It has been previously demonstrated that hepatocytes can be converted into insulin-producing β-like cells by introducing pancreatic transcription factors, indicating that direct hepatocyte reprogramming holds potential as a treatment for diabetes. However, the efficiency at which functional β-cells can be derived from hepatocyte reprogramming remains low. Here we demonstrated that the combination of Pdx1 and Ngn3 can trigger reprogramming of mouse and human liver cells to insulin-producing cells that exhibit the characteristics of pancreatic β-cells. Treatment with PDGF-AA was found to facilitate Pdx1 and Ngn3-induced reprogramming of hepatocytes to β-like cells with the ability to secrete insulin in response to glucose stimulus. Importantly, this reprogramming strategy could be applied to adult mouse primary hepatocytes, and the transplantation of β-like cells derived from primary hepatocyte reprogramming could ameliorate hyperglycemia in diabetic mice. These findings support the possibility of developing transplantation therapies for type 1 diabetes through the use of β-like cells derived from autologous hepatocyte reprogramming. ? 2016 Cognizant, LLC. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84991666166&doi=10.3727%2f096368916X691439&partnerID=40&md5=2d1445de043a87a05e21ac9555288ce2 https://scholars.lib.ntu.edu.tw/handle/123456789/545685 |
ISSN: | 0963-6897 | DOI: | 10.3727/096368916X691439 | SDG/關鍵字: | albumin; amylase; amylin; C peptide; cyclin dependent kinase 4; glucagon; glucagon like peptide 1; glyceraldehyde 3 phosphate dehydrogenase; inwardly rectifying potassium channel subunit Kir6.2; neurogenin 3; platelet derived growth factor; platelet derived growth factor A; platelet derived growth factor AA; proprotein convertase 1; somatostatin; transcription factor Nkx2.2; transcription factor PAX4; transcription factor PDX 1; transferrin; basic helix loop helix transcription factor; exendin 4; glucagon like peptide 1; glucagon like peptide 1 receptor; glucose; homeodomain protein; insulin; nerve protein; Neurog3 protein, mouse; pancreatic and duodenal homeobox 1 protein; peptide; platelet derived growth factor; platelet derived growth factor alpha receptor; platelet-derived growth factor A; transactivator protein; venom; animal cell; animal experiment; Article; cell lineage; cell transdifferentiation; controlled study; diabetes mellitus; enzyme linked immunosorbent assay; flow cytometry; gluconeogenesis; human; human cell; hyperglycemia; immunofluorescence test; insulin dependent diabetes mellitus; insulin release; insulin synthesis; internal ribosome entry site; liver cell; mouse; nonhuman; nuclear reprogramming; pancreas islet beta cell; pancreas islet transplantation; priority journal; protein expression; real time polymerase chain reaction; reverse transcription polymerase chain reaction; RNA isolation; signal transduction; Western blotting; analysis; animal; C57BL mouse; cell culture; chemically induced; cytology; drug effects; experimental diabetes mellitus; fluorescence microscopy; gene vector; genetics; glucose blood level; Institute for Cancer Research mouse; liver cell; metabolism; nuclear reprogramming; pancreas islet beta cell; pathology; secretion (process); transgenic mouse; transplantation; Animals; Basic Helix-Loop-Helix Transcription Factors; Blood Glucose; Cell Transdifferentiation; Cells, Cultured; Cellular Reprogramming; Diabetes Mellitus, Experimental; Genetic Vectors; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucose; Hepatocytes; Homeodomain Proteins; Humans; Insulin; Insulin-Secreting Cells; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Transgenic; Microscopy, Fluorescence; Nerve Tissue Proteins; Peptides; Platelet-Derived Growth Factor; Receptor, Platelet-Derived Growth Factor alpha; Trans-Activators; Venoms |
顯示於: | 醫學系 |
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