Karimi Samaneh, Ai Jafar, Khorsandi Layasadat, Bijan Nejad Darioush, Saki Ghasem
Cell and Molecular Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Tissue Engineering and Applied Cell Sciences, Department-School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Cell J. 2019 Jan;20(4):477-482. doi: 10.22074/cellj.2019.5542. Epub 2018 Aug 1.
Type 1 diabetes is caused by destruction of beta cells of pancreas. Vildagliptin (VG), a dipeptidyl peptidase IV (DPP IV) inhibitor, is an anti-diabetic drug, which increases beta cell mass. In the present study, the effects of VG on generation of insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ASCs) is investigated.
In this experimental study, ASCs were isolated and after characterization were exposed to differentiation media with or without VG. The presence of IPCs was confirmed by morphological analysis and gene expression (Pdx-1, Glut-2 and Insulin). Newport Green staining was used to determine insulin-positive cells. Insulin secretion under different concentrations of glucose was measured using radioimmunoassay method.
In the presence of VG the morphology of differentiated cells was similar to the pancreatic islet cells. Expression of Pdx-1, Glut-2 and Insulin genes in VG-treated cells was significantly higher than the cells exposed to induction media only. Insulin release from VG-treated ASCs showed a nearly 3.6 fold (P<0.05) increase when exposed to a highglucose medium in comparison to untreated ASCs. The percentage of insulin-positive cells in the VG-treated cells was approximately 2.9-fold higher than the untreated ASCs.
The present study has demonstrated that VG elevates differentiation of ASCs into IPCs. Improvement of this protocol may be used in cell therapy in diabetic patients.
1型糖尿病是由胰腺β细胞破坏引起的。维格列汀(VG)是一种二肽基肽酶IV(DPP IV)抑制剂,是一种抗糖尿病药物,可增加β细胞量。在本研究中,研究了VG对脂肪来源间充质干细胞(ASC)产生胰岛素生成细胞(IPC)的影响。
在本实验研究中,分离ASC并在鉴定后将其暴露于含或不含VG的分化培养基中。通过形态学分析和基因表达(Pdx-1、Glut-2和胰岛素)确认IPC的存在。使用纽波特绿染色法确定胰岛素阳性细胞。采用放射免疫分析法测定不同葡萄糖浓度下的胰岛素分泌。
在存在VG的情况下,分化细胞的形态与胰岛细胞相似。VG处理的细胞中Pdx-1、Glut-2和胰岛素基因的表达明显高于仅暴露于诱导培养基的细胞。与未处理的ASC相比,暴露于高糖培养基时,VG处理的ASC释放的胰岛素增加了近3.6倍(P<0.05)。VG处理的细胞中胰岛素阳性细胞的百分比比未处理的ASC高约2.9倍。
本研究表明,VG可提高ASC向IPC的分化。改进该方案可用于糖尿病患者的细胞治疗。