Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 16/10 Miklukho-Maklaya Str., 117997 Moscow, Russia.
National Medical Research Center of Obstetrics, Gynecology and Perinatology Named after Academician V. I. Kulakov of the Ministry of Health of the Russian Federation, 4 Oparina Str., 117997 Moscow, Russia.
Int J Mol Sci. 2022 Feb 15;23(4):2134. doi: 10.3390/ijms23042134.
Multiple studies have demonstrated that various nanoparticles (NPs) stimulate osteogenic differentiation of mesenchymal stem cells (MSCs) and inhibit adipogenic ones. The mechanisms of these effects are not determined. The aim of this paper was to estimate Wharton's Jelly MSCs phenotype and humoral factor production during tri-lineage differentiation per se and in the presence of silicon-gold NPs. Silicon (SiNPs), gold (AuNPs), and 10% Au-doped Si nanoparticles (SiAuNPs) were synthesized by laser ablation, characterized, and studied in MSC cultures before and during differentiation. Humoral factor production ( = 41) was analyzed by Luminex technology. NPs were nontoxic, did not induce ROS production, and stimulated G-CSF, GM-CSF, VEGF, CXCL1 (GRO) production in four day MSC cultures. During MSC differentiation, all NPs stimulated CD13 and CD90 expression in osteogenic cultures. MSC differentiation resulted in a decrease in multiple humoral factor production to day 14 of incubation. NPs did not significantly affect the production in chondrogenic cultures and stimulated it in both osteogenic and adipogenic ones. The major difference in the protein production between osteogenic and adipogenic MSC cultures in the presence of NPs was VEGF level, which was unaffected in osteogenic cells and 4-9 times increased in adipogenic ones. The effects of NPs decreased in a row AuNPs > SiAuNPs > SiNPs. Taken collectively, high expression of CD13 and CD90 by MSCs and critical level of VEGF production can, at least, partially explain the stimulatory effect of NPs on MSC osteogenic differentiation.
多项研究表明,各种纳米粒子(NPs)可刺激间充质干细胞(MSCs)的成骨分化,抑制其成脂分化。这些作用的机制尚不清楚。本文旨在评估Wharton 氏胶 MSC 在三系分化过程中的表型和体液因子产生情况,以及在硅-金纳米粒子(SiNPs)存在的情况下的情况。通过激光烧蚀合成了硅(SiNPs)、金(AuNPs)和 10%Au 掺杂硅纳米粒子(SiAuNPs),并对其进行了表征,然后在 MSC 培养物中进行了分化前和分化期间的研究。通过 Luminex 技术分析了体液因子的产生(n = 41)。NPs 无毒性,不会诱导 ROS 产生,并且在 4 天的 MSC 培养物中刺激 G-CSF、GM-CSF、VEGF、CXCL1(GRO)的产生。在 MSC 分化过程中,所有 NPs 均刺激成骨培养物中 CD13 和 CD90 的表达。MSC 分化导致在孵育的第 14 天,多种体液因子的产生减少。NPs 对软骨形成培养物的产生没有显著影响,但刺激了成骨和脂肪形成培养物的产生。在 NPs 存在下,成骨和脂肪形成 MSC 培养物之间蛋白产生的主要差异是 VEGF 水平,在成骨细胞中不受影响,而在脂肪形成细胞中增加了 4-9 倍。NPs 的作用呈 AuNPs > SiAuNPs > SiNPs 的顺序递减。总的来说,MSCs 高表达 CD13 和 CD90 以及关键水平的 VEGF 产生,至少可以部分解释 NPs 对 MSC 成骨分化的刺激作用。