Hormones Department, National Research Centre, Giza, Egypt; Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt.
Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt; Basic Dental Science Department, National Research Centre, Giza, Egypt.
Tissue Cell. 2021 Dec;73:101661. doi: 10.1016/j.tice.2021.101661. Epub 2021 Oct 7.
The development of efficient insulin producing cells (IPC) induction system is fundamental for the regenerative clinical applications targeting Diabetes Mellitus. This study was set to generate IPC from human dental pulp stem cells (hDPSCs) capable of surviving under hypoxic conditions in vitro and in vivo.
hDPSCs were cultured in IPCs induction media augmented with Cerium or Yttrium oxide nanoparticles along with selected growth factors & cytokines. The generated IPC were subjected to hypoxic stress in vitro to evaluate the ability of the nanoparticles to combat hypoxia. Next, they were labelled and implanted into diabetic rats. Twenty eight days later, blood glucose and serum insulin levels, hepatic hexokinase and glucose-6-phosphate dehydrogenase activities were measured. Pancreatic vascular endothelial growth factor (VEGF), pancreatic duodenal homeobox1 (Pdx-1), hypoxia inducible factor 1 alpha (HIF-1α) and Caspase-3 genes expression level were evaluated.
hDPSCs were successfully differentiated into IPCs after incubation with the inductive media enriched with nanoparticles. The generated IPCs released significant amounts of insulin in response to increasing glucose concentration both in vitro & in vivo. The generated IPCs showed up-regulation in the expression levels of anti-apoptotic genes in concomitant with down-regulation in the expression levels of hypoxic, and apoptotic genes. The in vivo study confirmed the homing of PKH-26-labeled cells in pancreas of treated groups. A significant up-regulation in the expression of pancreatic VEGF and PDX-1 genes associated with significant down-regulation in the expression of pancreatic HIF-1α and caspase-3 was evident.
The achieved results highlight the promising role of the Cerium & Yttrium oxide nanoparticles in promoting the generation of IPCs that have the ability to combat hypoxia and govern diabetes mellitus.
开发高效的胰岛素产生细胞（IPC）诱导系统是针对糖尿病的再生临床应用的基础。本研究旨在从人牙髓干细胞（hDPSCs）中生成能够在体外和体内缺氧条件下存活的 IPC。
将 hDPSCs 在 IPC 诱导培养基中培养，该培养基中加入了铈或钇氧化物纳米粒子以及选定的生长因子和细胞因子。生成的 IPC 在体外受到缺氧应激，以评估纳米粒子对抗缺氧的能力。然后，将它们标记并植入糖尿病大鼠体内。28 天后，测量血糖和血清胰岛素水平、肝己糖激酶和葡萄糖-6-磷酸脱氢酶活性。评估胰腺血管内皮生长因子（VEGF）、胰腺十二指肠同源盒 1（Pdx-1）、缺氧诱导因子 1α（HIF-1α）和 Caspase-3 基因的表达水平。
hDPSCs 在富含纳米粒子的诱导培养基中孵育后成功分化为 IPC。生成的 IPC 在体外和体内均能响应葡萄糖浓度的增加释放大量胰岛素。生成的 IPC 表现出抗凋亡基因表达水平的上调，同时伴随着缺氧和凋亡基因表达水平的下调。体内研究证实了 PKH-26 标记细胞在治疗组胰腺中的归巢。胰腺 VEGF 和 PDX-1 基因的表达显著上调，同时胰腺 HIF-1α 和 caspase-3 的表达显著下调。
研究结果突出了铈和钇氧化物纳米粒子在促进生成具有对抗缺氧和控制糖尿病能力的 IPC 方面的有前途的作用。
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