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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...

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Autores principales: Luo, Haizhao, Chen, Rongping, Yang, Rui, Liu, Yan, Chen, Youping, Shu, Yi, Chen, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
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.
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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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