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.
10.4093/dmj.2011.35.2.119
- Author:
Young Hye YOU
1
;
Dong Sik HAM
;
Heon Seok PARK
;
Marie RHEE
;
Ji Won KIM
;
Kun Ho YOON
Author Information
1. Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea. yoonk@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Ad-BETA2/NeuroD;
Ad-MafA;
Ad-PDX-1/VP16;
Beta-cell;
Neonatal pig cell clusters;
Pancreatic exocrine cell;
Transdifferentiation;
Transplantation
- MeSH:
Adenoviridae;
Adult;
Aged;
Animals;
Capsules;
Gene Expression;
Humans;
Immunohistochemistry;
Insulin;
Kidney;
Pancreas;
Stem Cells;
Swine;
Transplants
- From:Diabetes & Metabolism Journal
2011;35(2):119-129
- CountryRepublic of Korea
- Language:English
-
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.
