Mandal, Paulami; De, Debojyoti; Yun, Kyunghee; Kim, Kyeong Kyu published the artcile< Improved differentiation of human adipose stem cells to insulin-producing β-like cells using PDFGR kinase inhibitor Tyrphostin9>, Related Products of 452-06-2, the main research area is human insulin PDFGR kinase inhibitor adipose stem cell; Adipose-derived stem cells; Diabetes mellitus; Differentiation; PDGFR inhibitor; β-cell.
Diabetes mellitus (DM) is a metabolic syndrome where insulin secretion or the response to insulin produced by the body is compromised. The only available long-term treatment is the transplantation of pancreas or islet for procuring β-cells. However, due to the shortage of β-cell sources from the tissues, differentiation of pluripotent stem cells or terminally differentiated cells into β-cell is proposed as an alternative strategy. Previously, human adipose-derived stem cells (ADSCs) were reported to be converted into β-like cells by a stepwise treatment of chems. and growth factors. However, due to the low conversion efficiency, the clin. application was not feasible. In this study, we developed a modified conversion protocol with improved yield and functionality, which is achieved by changing the culture method and addition of Tyrphostin9, a platelet-derived growth factor receptor (PDGFR) kinase inhibitor. Tyrphostin9 was identified from a cell-based chem. screening using the mCherry reporter under the control of the Pdx1 promoter. The β-like cells differentiated under the new protocol showed a 3.6-fold increase in the expression of Pdx1, a marker for pancreatic differentiation, as compared to the previous protocol. We propose that Tyrphostin9 contributes to the β-like cell differentiation by playing a dual role; enhancing the definitive endoderm generation by inhibiting the PI3K signaling and suppressing the taurine-mediated proliferation of definitive endoderm. Importantly, these differentiated cells responded well to low and high glucose stimulations compared to cells differentiated by the previous protocol, as confirmed by the 2.0-fold increase in the C-peptide release. As ADSCs are abundant, easily isolated, and autologous in nature, improved differentiation approaches to generate β-like cells from ADSCs would provide a better opportunity for treating diabetes.
Biochemical and Biophysical Research Communications published new progress about Diabetes mellitus. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Related Products of 452-06-2.
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