Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand; Graduate Program in Veterinary Bioscience, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand; Research Unit of Mineralized Tissue, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
Research Unit of Mineralized Tissue, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
Biochem Biophys Res Commun. 2014 Sep 26;452(3):581-7. doi: 10.1016/j.bbrc.2014.08.121. Epub 2014 Aug 30.
Dental tissue-derived mesenchymal stem cells have been proposed as an alternative source for mesenchymal stem cells. Here, we investigated the differentiation ability toward insulin producing cells (IPCs) of human dental pulp stem cells (hDPSCs) and human periodontal ligament stem cells (hPDLSCs). These cells expressed mesenchymal stem cell surface markers and were able to differentiate toward osteogenic and adipogenic lineages. Upon 3 step-IPCs induction, hDPSCs exhibited more colony number than hPDLSCs. The mRNA upregulation of pancreatic endoderm/islet markers was noted. However, the significant increase was noted only for PDX-1, NGN-3, and INSULIN mRNA expression of hDPSCs. The hDPSCs-derived IPCs expressed PRO-INSULIN and released C-PEPTIDE upon glucose stimulation in dose-dependent manner. After IPCs induction, the Notch target, HES-1 and HEY-1, mRNA expression was markedly noted. Notch inhibition during the last induction step or throughout the protocol disturbed the ability of C-PEPTIDE release upon glucose stimulation. The results suggested that hDPSCs had better differentiation potential toward IPCs than hPDLSCs. In addition, the Notch signalling might involve in the differentiation regulation of hDPSCs into IPCs.
牙髓间充质干细胞已被提议作为间充质干细胞的替代来源。在这里,我们研究了人牙髓干细胞(hDPSCs)和人牙周膜干细胞(hPDLSCs)向胰岛素产生细胞(IPCs)分化的能力。这些细胞表达间充质干细胞表面标志物,并能向成骨细胞和成脂细胞谱系分化。在 3 步 IPCs 诱导后,hDPSCs 的集落数量比 hPDLSCs 更多。胰腺内胚层/胰岛标记物的 mRNA 上调。然而,hDPSCs 的 PDX-1、NGN-3 和 INSULIN mRNA 表达仅显著增加。hDPSCs 衍生的 IPCs 在葡萄糖刺激下以剂量依赖性方式表达 PRO-INSULIN 并释放 C-PEPTIDE。在 IPCs 诱导后,Notch 靶基因 HES-1 和 HEY-1 的 mRNA 表达明显。在最后一步诱导或整个方案期间抑制 Notch 会干扰葡萄糖刺激下 C-PEPTIDE 释放的能力。结果表明,hDPSCs 向 IPCs 分化的潜力优于 hPDLSCs。此外,Notch 信号通路可能参与 hDPSCs 向 IPCs 分化的调控。