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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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2014/716163 |
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| author | Haizhao Luo Rongping Chen Rui Yang Yan Liu Youping Chen Yi Shu Hong Chen |
| author_facet | Haizhao Luo Rongping Chen Rui Yang Yan Liu Youping Chen Yi Shu Hong Chen |
| author_sort | Haizhao Luo |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-1afcac1efee0410f9f4bdf2b3c097252 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-1afcac1efee0410f9f4bdf2b3c0972522025-02-03T05:54:22ZengWileyJournal of Diabetes Research2314-67452314-67532014-01-01201410.1155/2014/716163716163Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic VectorsHaizhao Luo0Rongping Chen1Rui Yang2Yan Liu3Youping Chen4Yi Shu5Hong Chen6Department of Endocrinology, Zhujiang Hospital, Southern Medical University, No. 253 Gong Ye Road, Guangzhou 510282, ChinaDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, No. 253 Gong Ye Road, Guangzhou 510282, ChinaDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, No. 253 Gong Ye Road, Guangzhou 510282, ChinaDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, No. 253 Gong Ye Road, Guangzhou 510282, ChinaDepartment of Endocrinology, Nanhai Hospital, Southern Medical University, No. 40 Foping Road, Foshan 528200, ChinaDepartment of Endocrinology, Nanhai Hospital, Southern Medical University, No. 40 Foping Road, Foshan 528200, ChinaDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, No. 253 Gong Ye Road, Guangzhou 510282, ChinaThe 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.http://dx.doi.org/10.1155/2014/716163 |
| spellingShingle | Haizhao Luo Rongping Chen Rui Yang Yan Liu Youping Chen Yi Shu Hong Chen Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors Journal of Diabetes Research |
| 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 |
| url | http://dx.doi.org/10.1155/2014/716163 |
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