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带不同电荷和部分的金纳米粒子诱导间充质干细胞成骨分化的差异细胞反应。

Gold nanoparticles with different charge and moiety induce differential cell response on mesenchymal stem cell osteogenesis.

机构信息

Tissue Regeneration Materials Unit, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

Tissue Regeneration Materials Unit, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

出版信息

Biomaterials. 2015 Jun;54:226-36. doi: 10.1016/j.biomaterials.2015.03.001. Epub 2015 Apr 6.

Abstract

Stem cells exist in an in vivo microenvironment that provides biological and physiochemical cues to direct cell fate decisions. How the stem cells sense and respond to these cues is still not clearly understood. Gold nanoparticles (AuNPs) have been widely used for manipulation of cell behavior due to their ease of synthesis and versatility in surface functionalization. In this study, AuNPs with amine (AuNP-NH2), carboxyl (AuNP-COOH) and hydroxyl (AuNP-OH) functional groups possessing different surface charge were synthesized. Human bone marrow-derived mesenchymal stem cells (hMSCs) were treated with the surface functionalized AuNPs and assessed for cell viability and osteogenic differentiation ability. The surface functionalized AuNPs were well tolerated by hMSCs and showed no acute toxicity. Positively charged AuNPs showed higher cellular uptake. AuNPs did not inhibit osteogenesis but ALP activity and calcium deposition were markedly reduced in AuNP-COOH treatment. Gene profiling revealed an upregulation of TGF-β and FGF-2 expression that promoted cell proliferation over osteogenic differentiation in hMSCs. These results provide some insight on the influence of surface functionalized AuNPs on hMSCs behavior and the use of these materials for strategic tissue engineering.

摘要

干细胞存在于体内微环境中,该微环境提供生物和物理化学线索,以指导细胞命运决策。干细胞如何感知和响应这些线索尚不清楚。由于金纳米粒子(AuNPs)易于合成且表面功能化具有多功能性,因此已被广泛用于操纵细胞行为。在这项研究中,合成了具有胺(AuNP-NH2)、羧基(AuNP-COOH)和羟基(AuNP-OH)官能团的 AuNPs,这些官能团具有不同的表面电荷。用人骨髓间充质干细胞(hMSCs)处理表面功能化的 AuNPs,并评估细胞活力和成骨分化能力。表面功能化的 AuNPs 被 hMSCs 很好地耐受,没有急性毒性。带正电荷的 AuNPs 表现出更高的细胞摄取率。AuNPs 并没有抑制成骨作用,但 AuNP-COOH 处理显著降低了碱性磷酸酶活性和钙沉积。基因谱分析显示,TGF-β和 FGF-2 的表达上调,促进了 hMSCs 中的细胞增殖而非成骨分化。这些结果提供了一些关于表面功能化 AuNPs 对 hMSCs 行为的影响的见解,并为这些材料在战略性组织工程中的应用提供了依据。

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