Generation of Functional Beta-Like Cells from Human Exocrine Pancreas
| العنوان: | Generation of Functional Beta-Like Cells from Human Exocrine Pancreas |
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| المؤلفون: | Yves Heremans, Maria João Lima, Hilary M. Docherty, John Casey, Harry Heimberg, Neil W. A. McGowan, Kenneth R. Muir, Kevin Docherty, Shareen Forbes |
| المساهمون: | Pathology/molecular and cellular medicine, Beta Cell Neogenesis |
| المصدر: | PLoS ONE, Vol 11, Iss 5, p e0156204 (2016) Lima, M J, Muir, K R, Docherty, H M, McGowan, N W A, Forbes, S, Heremans, Y, Heimberg, H, Casey, J & Docherty, K 2016, ' Generation of Functional Beta-Like Cells from Human Exocrine Pancreas ', PLoS ONE, vol. 11, no. 5, pp. e0156204 . https://doi.org/10.1371/journal.pone.0156204Test PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Peptide Hormones, medicine.medical_treatment, Cell- and Tissue-Based Therapy, lcsh:Medicine, Mice, SCID, Biochemistry, Mice, Endocrinology, 0302 clinical medicine, Insulin-Secreting Cells, Medicine and Health Sciences, Insulin, Paired Box Transcription Factors, Small interfering RNAs, Cellular Reprogramming Techniques, RNA, Small Interfering, lcsh:Science, Cells, Cultured, Proinsulin, Multidisciplinary, Organic Compounds, Monosaccharides, adenovirus, Pancreas, Exocrine, Insulin oscillation, Nucleic acids, Chemistry, medicine.anatomical_structure, Physical Sciences, Cytochemistry, PDX1, Female, RNA Interference, Somatostatin, Pancreas, Immunocytochemistry, Research Article, Adult, medicine.medical_specialty, endocrine system, Endocrine Disorders, Carbohydrates, Biology, Glucagon, Streptozocin, Diabetes Mellitus, Experimental, Young Adult, 03 medical and health sciences, Internal medicine, Diabetes Mellitus, Genetics, medicine, Adults, Animals, Humans, Non-coding RNA, exocrine cells, Diabetic Endocrinology, Homeodomain Proteins, Type 1 diabetes, Organic Chemistry, lcsh:R, Chemical Compounds, reprogramming, Biology and Life Sciences, Cell Biology, medicine.disease, Hormones, Gene regulation, Transplantation, beta cells, Glucose, 030104 developmental biology, Age Groups, Metabolic Disorders, People and Places, RNA, Population Groupings, lcsh:Q, Gene expression, 030217 neurology & neurosurgery, Transcription Factors |
| الوصف: | Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells. The efficiency was further increased by culture on laminin-coated plates in media containing low glucose concentrations. Immunocytochemistry revealed that reprogrammed cultures were composed of ~45% islet-like clusters comprising >80% monohormonal insulin+ cells. The resultant β-like cells expressed insulin protein levels at ~15-30% of that in adult human islets, efficiently processed proinsulin and packaged insulin into secretory granules, exhibited glucose responsive insulin secretion, and had an immediate and prolonged effect in normalising blood glucose levels upon transplantation into diabetic mice. We estimate that approximately 3 billion of these cells would have an immediate therapeutic effect following engraftment in type 1 diabetes patients and that one pancreas would provide sufficient tissue for numerous transplants. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::540fbede83f3d8407ae0d031b0c13c66Test http://europepmc.org/articles/PMC4887015?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....540fbede83f3d8407ae0d031b0c13c66 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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