Abstract
BackgroundInsulin-producing cells differentiated from human mesenchymal stem cells demonstrate limited glucose-stimulated insulin secretion. Cytochrome P450 2J2 and its product epoxyeicosatrienoic acids regulate β-cell function in the human pancreas. The aim of this study is to explore the expression pattern of cytochrome P450 2J2 gene and 14, 15 epoxyeicosatrienoic level along the differentiation of human bone marrow-derived mesenchymal stem cells into insulin-producing cells.ResultsThe differentiated insulin-producing cells express high levels of pancreatic duodenal homeobox-1 and insulin gene mRNA. It secretes increasing amounts of C-peptide in response to increasing glucose concentrations than undifferentiated cells. The differentiated insulin-producing cells were found to express reduced amounts of cytochrome P450 2J2 gene mRNA and significant low level of 14, 15 epoxyeicosatrienoic acid than the undifferentiated cells. A strong positive correlation between 14, 15 epoxyeicosatrienoic concentrations and C-peptide released from the differentiated insulin-producing cells was noticed.ConclusionsCytochrome P4502J2 and its product 14, 15 epoxyeicosatrienoic might affect insulin secretion from differentiated insulin-producing cells.
Highlights
Insulin-producing cells differentiated from human mesenchymal stem cells demonstrate limited glucose-stimulated insulin secretion
The generation of Insulin-producing cells (IPCs) from MSCs occurs at a low rate, and most of these induced cells show limited glucose-stimulated insulin secretion (GSIS), which limits basic and clinical applications (Xie et al 2013)
Validation of IPCs derived from HBM-MSCs P3 HBM-MSCs were induced to differentiate into IPCs by a three-step, 18-day protocol
Summary
Insulin-producing cells differentiated from human mesenchymal stem cells demonstrate limited glucose-stimulated insulin secretion. The aim of this study is to explore the expression pattern of cytochrome P450 2J2 gene and 14, 15 epoxyeicosatrienoic level along the differentiation of human bone marrow-derived mesenchymal stem cells into insulin-producing cells. Bone marrow-derived MSCs (BM-MSCs) can be differentiated into insulin-producing cells (IPCs). It is characterized by expressing both the pancreatic β-cell developmental genes as pancreatic duodenal homeobox-1 (PDX-1) gene, and functional genes as insulin and glucagon genes (Zanini et al 2011; Xie et the generation of IPCs from MSCs occurs at a low rate, and most of these induced cells show limited glucose-stimulated insulin secretion (GSIS), which limits basic and clinical applications (Xie et al 2013). EETs posse an anti-inflammatory effect via the suppression of NF-ĸB and IĸB kinase activity (Node et al 1999)
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