Silica Nanoparticle Internalization Improves Chemotactic Behaviour of Human Mesenchymal Stem Cells Acting on the SDF1α/CXCR4 Axis

Abstract

Human mesenchymal stem cell (hMSC)-based therapy is an emerging resource in regenerative medicine. Despite the innate ability of hMSCs to migrate to sites of injury, homing of infused hMSCs to the target tissue is inefficient. It was shown that silica nanoparticles (SiO2-NPs), previously developed to track the stem cells after transplantation, accumulated in lysosomes leading to a transient blockage of the autophagic flux. Since CXCR4 turnover is mainly regulated by autophagy, we tested the effect of SiO2-NPs on chemotactic migration of hMSCs along the SDF1α/CXCR4 axis that plays a pivotal role in directing MSC homing to sites of injury. Our results showed that SiO2-NP internalization augmented CXCR4 surface levels. We demonstrated that SiO2-NP-dependent CXCR4 increase was transient, and it reversed at the same time as lysosomal compartment normalization. Furthermore, the autophagy inhibitor Bafilomycin-A1 reproduced CXCR4 overexpression in control hMSCs confirming the direct effect of the autophagic degradation blockage on CXCR4 expression. Chemotaxis assays showed that SiO2-NPs increased hMSC migration toward SDF1α. In contrast, migration improvement was not observed in TNFα/TNFR axis, due to the proteasome-dependent TNFR regulation. Overall, our findings demonstrated that SiO2-NP internalization increases the chemotactic behaviour of hMSCs acting on the SDF1α/CXCR4 axis, unmasking a high potential to improve hMSC migration to sites of injury and therapeutic efficacy upon cell injection in vivo.

Enhancing mesenchymal stem cell survival and homing capability to improve cell engraftment efficacy for liver diseases

“…Similarly, Vitale et al . developed silica nanoparticles (SiO 2 -NPs) for MSC tracking and found that their internalization enhanced MSC migration by increasing CXCR-4 expression [ 92 ]. Hence, silica nanoparticle labeling is a novel method for improving the homing capabilities of MSCs.…”

Interaction of Graphene Oxide Nanoparticles with Human Mesenchymal Stem Cells Visualized in the Cell-IQ System

“…The decrease in velocity was shown to be positively correlated with the concentration of capsules in the medium during incubation. At the same time, some studies have shown the ability of nanoparticles to accumulate in endosomes, leading to a change in cellular metabolism, stimulation of cells, and an increase in their mobility [ 44 ]. In this study, it was shown that incubation of cells with P-GOb and bP-GOb samples resulted in an increase in cell velocity, which may indicate that these particles have some effect on cellular metabolism, although the mechanism of this effect is not clear at present.…”

Nanoparticles and Mesenchymal Stem Cell (MSC) Therapy for Cancer Treatment: Focus on Nanocarriers and a si-RNA CXCR4 Chemokine Blocker as Strategies for Tumor Eradication In Vitro and In Vivo

“…These chemotaxis assays demonstrated that SiO 2 -NPs enhanced hMSC migration toward SDF 1 alpha levels. Collectively, SiO 2 -NP internalization induces MCS chemotaxis via CXCR4/SDF1 alpha signaling in vitro [169,170].…”