Diabetes & Metabolism Journal

Original Articles

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

3,919 View
37 Download
9 Crossref

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

PDX-1/VP16 Overexpression Induce the Transdifferentiation of Canine Adult Pancreatic Cells into Beta-cells.: Young Hye You, Sun Cheol Park, Seung Hwan Lee, Heon Seok Park, Dong Sik Ham, Marie Rhee, Ji Won Kim, Ki Ho Song, Kun Ho Yoon; Korean Diabetes J. 2007;31(1):51-62. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.51

2,268 View
21 Download
3 Crossref

Abstract PDF

BACKGROUND
A major obstacle of islet transplantation is an inadequate supply of insulin-producing tissue. Ad-PDX-1/VP16 overexpression and Exendin-4 treatment have been proved the effects on differentiation and proliferation of pancreatic stem cells. But, the study is insufficient using adult animal pancreatic stem cells. METHODS: Pancreatic cells were prepared from the non-endocrine fraction of canine pancreases. This cells were cultivated free floating state and monolayer culture after dispersion. The floating pancreatic cells were transplanted under the kidney capsule of normoglycaemic nude mice. The dispersed pancreatic cells were infected with Ad-PDX-1/VP16 or Ad-GFP. After infection, those cells were transplanted of nude mice. After transplantation, mice were treated with either 1 nmol/kg exendin-4 or saline solution by intraperitoneal injection for 10 days. RESULTS: The relative volume of the beta-cells in the grafts of the free floating cultured pancreatic cells were 23.4 +/- 13.1% at two weeks and 5.2 +/- 2.0% at eight weeks. At two weeks after transplantation, the relative volume of insulin-positive cells in the grafts of dispersed pancreatic cells were 28 +/- 5.7%, 20.5 +/- 0.7% and 31 +/- 1.4% in control, GFP and PDX-1/VP16 treated groups respectively. At eight weeks after transplantation, the relative volume of insulin-positive cells in the grafts were 11.8 +/- 5.9%, 8 +/- 7.3% and 16.6 +/- 7.4% in control, GFP and PDX-1/VP16 treated groups respectively. Exendin-4 treatment didn't show any additive effects on transdifferentiation of pancreas stem cell into beta-cells. CONCLUSION: The expansion and transdifferentiation were not observed after the transplantation of the free floating cultured pancreatic cells. PDX-1/VP16 overexpression induces the transdifferentiation of adult pancreatic cells into beta-cells. However Exendin-4 treatment hasn't any effects on the expansion and transdifferentiation of the cells in the grafts.

Citations

Citations to this article as recorded by

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
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 & Metabolism Journal.2011; 35(2): 119. CrossRef
Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells
Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Sung-Dae Moon, Ki-Ho Song
Korean Diabetes Journal.2009; 33(6): 475. CrossRef

The Effects of Dexamethasone on the Expansion and Transdifferentiation of Transplanted Porcine Neonatal Pancreas Cell Clusters into beta-cells in Normal Nude Mice.: Ji Hun Yang, Sun Hee Suh, Sung Yoon Jeon, Oak Kee Hong, Kun Ho Yoon; Korean Diabetes J. 2004;28(5):356-366. Published online October 1, 2004

985 View
25 Download

Abstract PDF: BACKGROUND
Several studies have suggested that glucocorticoid has an influence on the development and function of the -cells. Thus, we undertook this study to determine whether exposure to dexamethasone (Dx) has an influence on the expansion or transdifferentiation of transplanted porcine NPCCs. METHODS: After transplantation (Tx) of 4,000 islet equivalents (IEQs) of porcine NPCCs into normal nude mice, Dx (1mg/kg) or the control vehicle were injected daily for 10 weeks. To clarify the effects of timing and duration of the Dx, one group was treated by Dx at the first 2 weeks (n=10) and the other group was treated later 8 weeks (n=10) during the 10 weeks treatment period. Thr total graft and beta-cell masses were determined by morphometric analysis. We preformed semi-quantitative RT-PCR for evaluating the pancreas transcription factors. RESULTS: The relative volume and absolute mass of the beta-cells and the total graft were significantly decreased by 10 weeks Dx treatment. Moreover, Dx treatment at thr first 2 weeks (n=10) also significantly decreased the total graft mass and absolute mass of the beta-cells. The relative volume of the beta-cells was negatively correlated and the area of the duct cysts was positively correlated with the duration of the Dx treatment. Pancreas transcription factors including PDX1, Ngn 3, ISL1 and NKx6.1 were decreased in the graft by 2 days treatment of Dx. CONCLUSION: These results suggest that Dx treatment suppresses the expansion and transdifferentiation of transplanted pancreas precursor cells into beta-cell.

First
Prev
Page of 1
Next
Last

Search