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Heparin mimics and fibroblast growth factor-2 fabricated nanogold composite in promoting neural differentiation of mouse embryonic stem cells.
Journal of Biomaterials Science, Polymer Edition ( IF 3.6 ) Pub Date : 2020-05-27 , DOI: 10.1080/09205063.2020.1767375
Fei Yu 1 , Shaoyu Cheng 1 , Jiehua Lei 1 , Yingjie Hang 1 , Qi Liu 1 , Hongwei Wang 1 , Lin Yuan 1
Affiliation  

The replacement therapy or transplantation using neural cells, which differentiated from stem cells, has emerged as a promising strategy for repairing damaged neural tissues and helping functional recovery in the treatment of neural system diseases. The challenge, however, is how to control embryonic stem cell fate so that neural differentiation can be efficiently directed to enrich a neuron cell population, and meanwhile to maintain their bioactivities. This is a key question and has a very significant impact in regenerative medicine. Here we proposed a new neural-differentiation inductive nanocomposite, containing gold nanoparticles (AuNPs), poly(2-methacrylamido glucopyranose-co-3-sulfopropyl acrylate) (PMS), and basic fibroblast growth factor (FGF2), for the high efficient directional neural-specific differentiation of mouse embryonic stem cells (mESCs). In this AuNP-PMS/FGF2 composite, PMS, playing as the high-active mimic of heparin/heparan sulfate (HS), is covalently anchored to AuNPs and bound with FGF2 on the surface of nanoparticles, forming a HS/FGF2 complex nanomimics to facilitate its binding to FGF receptor (FGFR) and promote high neural-inductive activity of mESCs. The stability, bioactivity and biocompatibility of the composite are investigated in this study. The results showed that the AuNP-PMS/FGF2 composite could maintain a long-term stability at room temperature for at least 8 days, and greatly promote the neural differentiation of mESCs. Compared with the other materials, the AuNP-PMS/FGF2 composite could significantly stimulate the expression of the specific neural differentiation markers (nestin and β3-tubulin), while obviously down-regulate the mRNA production of pluripotency marker Oct-4 in mESCs. Moreover, the promotion effect of the composite on neuronal maturation marker β3-tubulin expression achieved maximally at the low concentration of FGF2 (4 ng/mL), which suggested the high efficiency of AuNP-PMS/FGF2 composite in neural differentiation of mESCs. Meanwhile, both mESCs and L929 cells showed desirable growth during the incubation with AuNP-PMS/FGF2 composite. The AuNP-PMS/FGF2 system presents a new way to achieve HS/FGF2 complex nanomimics efficiently for the neural differentiation of mESCs.



中文翻译:

肝素模拟物和成纤维细胞生长因子-2 制造的纳米金复合物促进小鼠胚胎干细胞的神经分化。

使用从干细胞分化而来的神经细胞的替代疗法或移植已成为修复受损神经组织和帮助神经系统疾病治疗中功能恢复的有前途的策略。然而,挑战在于如何控制胚胎干细胞的命运,以便能够有效地引导神经分化以丰富神经元细胞群,同时保持其生物活性。这是一个关键问题,对再生医学具有非常重要的影响。在这里,我们提出了一种新的神经分化感应纳米复合材料,含有金粒子(AuNPs),聚(2-甲基丙烯酰胺glucopyranose--3-磺丙基丙烯酸酯) (PMS) 和碱性成纤维细胞生长因子 (FGF2),用于小鼠胚胎干细胞 (mESC) 的高效定向神经特异性分化。在这种 AuNP-PMS/FGF2 复合材料中,PMS 作为肝素/硫酸乙酰肝素 (HS) 的高活性模拟物,共价锚定在 AuNPs 上并与纳米颗粒表面的 FGF2 结合,形成 HS/FGF2 复合纳米模拟物促进其与 FGF 受体 (FGFR) 的结合并促进 mESC 的高神经诱导活性。本研究对复合材料的稳定性、生物活性和生物相容性进行了研究。结果表明,AuNP-PMS/FGF2复合材料在室温下可保持至少8天的长期稳定性,极大地促进了mESCs的神经分化。与其他材料相比,AuNP-PMS/FGF2复合物可以显着刺激特定神经分化标志物(巢蛋白和β3-微管蛋白)的表达,同时明显下调mESCs中多能性标志物Oct-4的mRNA产生。此外,该复合物对神经元成熟标志物 β3-微管蛋白表达的促进作用在低浓度 FGF2 (4 ng/mL) 下达到最大,这表明 AuNP-PMS/FGF2 复合物在 mESC 神经分化中的高效性。同时,mESCs 和 L929 细胞在与 AuNP-PMS/FGF2 复合物孵育期间均显示出理想的生长。AuNP-PMS/FGF2 系统提供了一种有效实现 HS/FGF2 复合纳米模拟物的新方法,用于 mESC 的神经分化。同时明显下调 mESC 中多能性标记物 Oct-4 的 mRNA 产生。此外,该复合物对神经元成熟标志物 β3-微管蛋白表达的促进作用在低浓度 FGF2 (4 ng/mL) 下达到最大,这表明 AuNP-PMS/FGF2 复合物在 mESC 神经分化中的高效性。同时,mESCs 和 L929 细胞在与 AuNP-PMS/FGF2 复合物孵育期间均显示出理想的生长。AuNP-PMS/FGF2 系统提供了一种有效实现 HS/FGF2 复合纳米模拟物的新方法,用于 mESC 的神经分化。同时明显下调 mESC 中多能性标记物 Oct-4 的 mRNA 产生。此外,该复合物对神经元成熟标志物 β3-微管蛋白表达的促进作用在低浓度 FGF2 (4 ng/mL) 下达到最大,这表明 AuNP-PMS/FGF2 复合物在 mESC 神经分化中的高效性。同时,mESCs 和 L929 细胞在与 AuNP-PMS/FGF2 复合物孵育期间均显示出理想的生长。AuNP-PMS/FGF2 系统提供了一种有效实现 HS/FGF2 复合纳米模拟物的新方法,用于 mESC 的神经分化。这表明 AuNP-PMS/FGF2 复合物在 mESCs 神经分化中的高效性。同时,mESCs 和 L929 细胞在与 AuNP-PMS/FGF2 复合物孵育期间均显示出理想的生长。AuNP-PMS/FGF2 系统提供了一种有效实现 HS/FGF2 复合纳米模拟物的新方法,用于 mESC 的神经分化。这表明 AuNP-PMS/FGF2 复合物在 mESCs 神经分化中的高效性。同时,mESCs 和 L929 细胞在与 AuNP-PMS/FGF2 复合物孵育期间均显示出理想的生长。AuNP-PMS/FGF2 系统提供了一种有效实现 HS/FGF2 复合纳米模拟物的新方法,用于 mESC 的神经分化。

更新日期:2020-05-27
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