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Cell Journal، جلد ۲۳، شماره ۶، صفحات ۶۳۳-۶۳۹
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چکیده فارسی مقاله
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عنوان انگلیسی Induction of ß Cell Replication by Small Molecule-Mediated Menin Inhibition and Combined PKC Activation and TGF-ß Inhibition as Revealed by A Refined Primary Culture Screening
چکیده انگلیسی مقاله Objective
Pancreatic β cells are recognized as central players in the pathogenesis of types 1 and 2 diabetes. Efficient and robust primary culture methods are required to interrogate β cell biology and screen potential anti-diabetic therapeutics. The aim of this study was to refine monolayer culture of beta cells and to investigate potential inducers of beta cell proliferation.
Materials and Methods
In this experimental study, we compared different culture methods to optimize conditions required for a monolayer culture of rat pancreatic islet cells in order to facilitate image analysis-based assays. We also used the refined culture method to screen a group of rationally selected candidate small molecules and their combinations to determine their potential proliferative effects on the β cells.
Results
Ham’s F10 medium supplemented with 2% foetal bovine serum (FBS) in the absence of any surface coating provided a superior monolayer β cell culture, while other conditions induced fibroblast-like cell growth or multilayer cell aggregation over two weeks. Evaluation of candidate small molecules showed that a menin inhibitor MI-2 and a combination of transforming growth factor-β (TGF-β) inhibitor SB481542 and protein kinase C (PKC) activator indolactam V (IndV) significantly induced replication of pancreatic β cells.
Conclusion
Overall, our optimized culture condition provided a convenient approach to study the cultured pancreatic islet cells and enabled us to detect the proliferative effect of menin inhibition and combined TGF-β inhibition and PKC activation, which could be considered as potential strategies for inducing β cell proliferation and regeneration.
کلیدواژه‌های انگلیسی مقاله Menin, Pancreatic β Cells, Proliferation, Protein kinase C, Transforming Growth Factor, β
نویسندگان مقاله Saghar Pahlavanneshan |
.Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Mehrdad Behmanesh |
.Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Yaser Tahamtani |
.. Department of Stem Cells and Developmental Biology, Cell Science Research Centre, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

Ensiyeh Hajizadeh-Saffar |
.Department of Regenerative Medicine, Cell Science Research Centre, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

Mohsen Basiri |
.. Department of Stem Cells and Developmental Biology, Cell Science Research Centre, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

نشانی اینترنتی https://www.celljournal.org/article_250756_97360b2991e506b6a02225ec1da94f83.pdf
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