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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
Article de En | WPRIM | ID: wpr-187625
Bibliothèque responsable: WPRO
ABSTRACT
BACKGROUND: A 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. METHODS: Adult 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. RESULTS: The 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. CONCLUSION: These 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.
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Mots clés
Texte intégral: 1 Indice: WPRIM Sujet Principal: Pancréas / Cellules souches / Suidae / Capsules / Immunohistochimie / Expression des gènes / Adenoviridae / Transplants / Insuline / Rein Limites du sujet: Animals / Humans langue: En Texte intégral: Diabetes & Metabolism Journal Année: 2011 Type: Article
Texte intégral: 1 Indice: WPRIM Sujet Principal: Pancréas / Cellules souches / Suidae / Capsules / Immunohistochimie / Expression des gènes / Adenoviridae / Transplants / Insuline / Rein Limites du sujet: Animals / Humans langue: En Texte intégral: Diabetes & Metabolism Journal Année: 2011 Type: Article