Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells
BackgroundA limitation in the number of insulin-producing pancreatic beta-cells is a special feature of diabetes. The identification of alternative sources for the induction of insulin-producing surrogate beta-cells is a matter of profound importance. PDX-1/VP16, BETA2/NeuroD, and MafA overexpressio...
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| Format: | Article |
| Language: | English |
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Korean Diabetes Association
2011-04-01
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| Series: | Diabetes & Metabolism Journal |
| Subjects: | |
| Online Access: | http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-35-119.pdf |
| _version_ | 1818319652954046464 |
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| author | Young-Hye You Dong-Sik Ham Heon-Seok Park Marie Rhee Ji-Won Kim Kun-Ho Yoon |
| author_facet | Young-Hye You Dong-Sik Ham Heon-Seok Park Marie Rhee Ji-Won Kim Kun-Ho Yoon |
| author_sort | Young-Hye You |
| collection | DOAJ |
| description | BackgroundA limitation in the number of insulin-producing pancreatic beta-cells is a special feature of diabetes. The identification of alternative sources for the induction of insulin-producing surrogate beta-cells is a matter of profound importance. PDX-1/VP16, BETA2/NeuroD, and MafA overexpression have been shown to influence the differentiation and proliferation of pancreatic stem cells. However, few studies have been conducted using adult animal pancreatic stem cells.MethodsAdult pig pancreatic cells were prepared from the non-endocrine fraction of adult pig pancreata. Porcine neonatal pancreas cell clusters (NPCCs) were prepared from neonatal pigs aged 1-2 days. The dispersed pancreatic cells were infected with PDX-1/VP16, BETA2/NeuroD, and MafA adenoviruses. After infection, these cells were transplanted under the kidney capsules of normoglycemic nude mice.ResultsThe adenovirus-mediated overexpression of PDX-1, BETA2/NeuroD and MafA induced insulin gene expression in NPCCs, but not in adult pig pancreatic cells. Immunocytochemistry revealed that the number of insulin-positive cells in NPCCs and adult pig pancreatic cells was approximately 2.6- and 1.1-fold greater than those in the green fluorescent protein control group, respectively. At four weeks after transplantation, the relative volume of insulin-positive cells in the grafts increased in the NPCCs, but not in the adult porcine pancreatic cells.ConclusionThese data indicate that PDX-1, BETA2/NeuroD, and MafA facilitate the beta-cell differentiation of NPCCs, but not adult pig pancreatic cells. Therefore PDX-1, BETA2/NeuroD, and MafA-induced NPCCs can be considered good sources for the induction of pancreatic beta-cells, and may also have some utility in the treatment of diabetes. |
| first_indexed | 2024-12-13T10:12:32Z |
| format | Article |
| id | doaj.art-0e33e6e34b5f4843ba034d8b1364464f |
| institution | Directory Open Access Journal |
| issn | 2233-6079 2233-6087 |
| language | English |
| last_indexed | 2024-12-13T10:12:32Z |
| publishDate | 2011-04-01 |
| publisher | Korean Diabetes Association |
| record_format | Article |
| series | Diabetes & Metabolism Journal |
| spelling | doaj.art-0e33e6e34b5f4843ba034d8b1364464f2022-12-21T23:51:22ZengKorean Diabetes AssociationDiabetes & Metabolism Journal2233-60792233-60872011-04-0135211912910.4093/dmj.2011.35.2.1192776Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-CellsYoung-Hye YouDong-Sik HamHeon-Seok ParkMarie RheeJi-Won KimKun-Ho YoonBackgroundA limitation in the number of insulin-producing pancreatic beta-cells is a special feature of diabetes. The identification of alternative sources for the induction of insulin-producing surrogate beta-cells is a matter of profound importance. PDX-1/VP16, BETA2/NeuroD, and MafA overexpression have been shown to influence the differentiation and proliferation of pancreatic stem cells. However, few studies have been conducted using adult animal pancreatic stem cells.MethodsAdult pig pancreatic cells were prepared from the non-endocrine fraction of adult pig pancreata. Porcine neonatal pancreas cell clusters (NPCCs) were prepared from neonatal pigs aged 1-2 days. The dispersed pancreatic cells were infected with PDX-1/VP16, BETA2/NeuroD, and MafA adenoviruses. After infection, these cells were transplanted under the kidney capsules of normoglycemic nude mice.ResultsThe adenovirus-mediated overexpression of PDX-1, BETA2/NeuroD and MafA induced insulin gene expression in NPCCs, but not in adult pig pancreatic cells. Immunocytochemistry revealed that the number of insulin-positive cells in NPCCs and adult pig pancreatic cells was approximately 2.6- and 1.1-fold greater than those in the green fluorescent protein control group, respectively. At four weeks after transplantation, the relative volume of insulin-positive cells in the grafts increased in the NPCCs, but not in the adult porcine pancreatic cells.ConclusionThese data indicate that PDX-1, BETA2/NeuroD, and MafA facilitate the beta-cell differentiation of NPCCs, but not adult pig pancreatic cells. Therefore PDX-1, BETA2/NeuroD, and MafA-induced NPCCs can be considered good sources for the induction of pancreatic beta-cells, and may also have some utility in the treatment of diabetes.http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-35-119.pdfAd-BETA2/NeuroDAd-MafAAd-PDX-1/VP16Beta-cellNeonatal pig cell clustersPancreatic exocrine cellTransdifferentiationTransplantation |
| spellingShingle | Young-Hye You Dong-Sik Ham Heon-Seok Park Marie Rhee Ji-Won Kim Kun-Ho Yoon Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells Diabetes & Metabolism Journal Ad-BETA2/NeuroD Ad-MafA Ad-PDX-1/VP16 Beta-cell Neonatal pig cell clusters Pancreatic exocrine cell Transdifferentiation Transplantation |
| title | Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells |
| title_full | Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells |
| title_fullStr | Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells |
| title_full_unstemmed | Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells |
| title_short | Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells |
| title_sort | adenoviruses expressing pdx 1 beta2 neurod and mafa induces the transdifferentiation of porcine neonatal pancreas cell clusters and adult pig pancreatic cells into beta cells |
| topic | Ad-BETA2/NeuroD Ad-MafA Ad-PDX-1/VP16 Beta-cell Neonatal pig cell clusters Pancreatic exocrine cell Transdifferentiation Transplantation |
| url | http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-35-119.pdf |
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