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Dong-Sik Ham  (Ham DS) 1 Article
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
Young-Hye You, Dong-Sik Ham, Heon-Seok Park, Marie Rhee, Ji-Won Kim, Kun-Ho Yoon
Diabetes Metab J. 2011;35(2):119-129.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.119
  • 3,686 View
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  • 9 Crossref
AbstractAbstract PDFPubReader   
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.

Citations

Citations to this article as recorded by  
  • The pig pangenome provides insights into the roles of coding structural variations in genetic diversity and adaptation
    Zhengcao Li, Xiaohong Liu, Chen Wang, Zhenyang Li, Bo Jiang, Ruifeng Zhang, Lu Tong, Youping Qu, Sheng He, Haifan Chen, Yafei Mao, Qingnan Li, Torsten Pook, Yu Wu, Yanjun Zan, Hui Zhang, Lu Li, Keying Wen, Yaosheng Chen
    Genome Research.2023; 33(10): 1833.     CrossRef
  • Improvement of the therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet
    Yu Na Lee, Hye-Jin Yi, Eun Hye Seo, Jooyun Oh, Song Lee, Sarah Ferber, Teruo Okano, In Kyong Shim, Song Cheol Kim
    Stem Cell Research & Therapy.2021;[Epub]     CrossRef
  • Generation of iPSC-derived insulin-producing cells from patients with type 1 and type 2 diabetes compared with healthy control
    Min Jung Kim, Eun Young Lee, Young-Hye You, Hae Kyung Yang, Kun-Ho Yoon, Ji-Won Kim
    Stem Cell Research.2020; 48: 101958.     CrossRef
  • Effect of FIGF overexpression on liver cells transforming to insulin-producing cells
    Yaqin He, Xiaoliang Xie, Xiaoyan Li, Shikuo Rong, Yukui Li, Zhenhui Lu
    Journal of Biosciences.2019;[Epub]     CrossRef
  • Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD
    So-Hyun Lee, Marie Rhee, Ji-Won Kim, Kun-Ho Yoon
    Diabetes & Metabolism Journal.2017; 41(5): 405.     CrossRef
  • Quantitative Raman spectral changes of the differentiation of mesenchymal stem cells into islet-like cells by biochemical component analysis and multiple peak fitting
    Xin Su, Shaoyin Fang, Daosen Zhang, Qinnan Zhang, Yingtian He, Xiaoxu Lu, Shengde Liu, Liyun Zhong
    Journal of Biomedical Optics.2015; 20(12): 125002.     CrossRef
  • Generation of Functional Insulin-Producing Cells from Neonatal Porcine Liver-Derived Cells by PDX1/VP16, BETA2/NeuroD and MafA
    Dong-Sik Ham, Juyoung Shin, Ji-Won Kim, Heon-Seok Park, Jae-Hyoung Cho, Kun-Ho Yoon, Kathrin Maedler
    PLoS ONE.2013; 8(11): e79076.     CrossRef
  • PPARγ Activation Attenuates Glycated-Serum Induced Pancreatic Beta-Cell Dysfunction through Enhancing Pdx1 and Mafa Protein Stability
    Yunxia Zhu, Ai Ma, Hongxiu Zhang, Chaojun Li, Rebecca Berdeaux
    PLoS ONE.2013; 8(2): e56386.     CrossRef
  • β‐Cell differentiation and regeneration in type 1 diabetes
    L. Ding, C. Gysemans, C. Mathieu
    Diabetes, Obesity and Metabolism.2013; 15(s3): 98.     CrossRef

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