Silicon-Gold Nanoparticles Affect Wharton's Jelly Phenotype and Secretome during Tri-Lineage Differentiation.

Elena V Svirshchevskaya,Anton A Popov,Rimma A Poltavtseva,Vladimir A Oleinikov,Svetlana V Sizova,Ivan V Bogdanov,Daria O Solovyeva,Anton E Efimov,Mariya V Konovalova,Nina V Sharonova

doi:10.3390/ijms23042134

Abstract

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 (n = 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.

Highlights

Recent advances in nanotherapeutics provide diverse groups of synthetic nanoparticles (NPs) and other types of nanomaterials
NPs were obtained by the method of pulsed laser ablation in liquid (PLAL) [27,28,29]
The targets were rotated during PLAL in order to ensure homogenous ablation (Figure 1a)

Summary

Introduction

Recent advances in nanotherapeutics provide diverse groups of synthetic nanoparticles (NPs) and other types of nanomaterials. Intravenous injection of NPs results in their accumulation in the liver [1,2,3], damaging epithelial and Kupfer’s cells. Liver as well as other organ regeneration depends on the functional potential of tissue stem cells. Mesenchymal stem cells (MSCs), which can be obtained from different tissues, are used as in vitro mimics of stem cells. MSCs are characterized by a set of specific surface marker, the ability to adhere to plastic, and to differentiate into different lineages depending on the factors. Multiple papers have demonstrated that different NPs affect the MSCs’ ability to differentiate into osteogetic and adipogenic lineages. Most consistent results show a stimulation of the osteogenic differentiation [4,5,6,7] and a suppression of the adipogenic one [7,8]. The chondrogenic differentiation of MSCs is likely to be unaffected by NPs as direct data are scarce [9]

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