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Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors
The neogenesis of insulin-producing cells (IPCs) from non-beta-cells has emerged as a potential method for treating diabetes mellitus (DM). Many groups have documented that activation of pancreatic transcription factor(s) in hepatocytes can improve the hyperglycemia in diabetic mice. In the present...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070478/ https://www.ncbi.nlm.nih.gov/pubmed/25006589 http://dx.doi.org/10.1155/2014/716163 |
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author | Luo, Haizhao Chen, Rongping Yang, Rui Liu, Yan Chen, Youping Shu, Yi Chen, Hong |
author_facet | Luo, Haizhao Chen, Rongping Yang, Rui Liu, Yan Chen, Youping Shu, Yi Chen, Hong |
author_sort | Luo, Haizhao |
collection | PubMed |
description | The neogenesis of insulin-producing cells (IPCs) from non-beta-cells has emerged as a potential method for treating diabetes mellitus (DM). Many groups have documented that activation of pancreatic transcription factor(s) in hepatocytes can improve the hyperglycemia in diabetic mice. In the present study, we explored a novel protocol that reprogrammed primary hepatocytes into functional IPCs by using multicistronic vectors carrying pancreatic and duodenal homeobox-1 (Pdx1), neurogenin 3 (Ngn3), and v-musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). These triple-transfected cells activated multiple beta-cell genes, synthesized and stored considerable amounts of insulin, and released the hormone in a glucose-regulated manner in vitro. Furthermore, when transplanted into streptozotocin-induced diabetic mice, the cells markedly ameliorated glucose tolerance. Our results indicated that ectopic expression of Pdx1, Ngn3, and MafA facilitated hepatocytes-to-IPCs reprogramming. This approach may offer opportunities for treatment of DM. |
format | Online Article Text |
id | pubmed-4070478 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-40704782014-07-08 Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors Luo, Haizhao Chen, Rongping Yang, Rui Liu, Yan Chen, Youping Shu, Yi Chen, Hong J Diabetes Res Research Article The neogenesis of insulin-producing cells (IPCs) from non-beta-cells has emerged as a potential method for treating diabetes mellitus (DM). Many groups have documented that activation of pancreatic transcription factor(s) in hepatocytes can improve the hyperglycemia in diabetic mice. In the present study, we explored a novel protocol that reprogrammed primary hepatocytes into functional IPCs by using multicistronic vectors carrying pancreatic and duodenal homeobox-1 (Pdx1), neurogenin 3 (Ngn3), and v-musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). These triple-transfected cells activated multiple beta-cell genes, synthesized and stored considerable amounts of insulin, and released the hormone in a glucose-regulated manner in vitro. Furthermore, when transplanted into streptozotocin-induced diabetic mice, the cells markedly ameliorated glucose tolerance. Our results indicated that ectopic expression of Pdx1, Ngn3, and MafA facilitated hepatocytes-to-IPCs reprogramming. This approach may offer opportunities for treatment of DM. Hindawi Publishing Corporation 2014 2014-05-19 /pmc/articles/PMC4070478/ /pubmed/25006589 http://dx.doi.org/10.1155/2014/716163 Text en Copyright © 2014 Haizhao Luo et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Luo, Haizhao Chen, Rongping Yang, Rui Liu, Yan Chen, Youping Shu, Yi Chen, Hong Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors |
title | Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors |
title_full | Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors |
title_fullStr | Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors |
title_full_unstemmed | Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors |
title_short | Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors |
title_sort | reprogramming of mice primary hepatocytes into insulin-producing cells by transfection with multicistronic vectors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070478/ https://www.ncbi.nlm.nih.gov/pubmed/25006589 http://dx.doi.org/10.1155/2014/716163 |
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