Human mesenchymal stem cells labelled with dye-loaded amorphous silica nanoparticles: long-term biosafety, stemness preservation and traceability in the beating heart

Abstract

BackgroundTreatment of myocardial infarction with mesenchymal stem cells (MSCs) has proven beneficial effects in both animal and clinical studies. Engineered silica nanoparticles (SiO2-NPs) have been extensively used as contrast agents in regenerative medicine, due to their resistance to degradation and ease of functionalization. However, there are still controversies on their effective biosafety on cellular systems. In this perspective, the aims of the present study are: 1) to deeply investigate the impact of amorphous 50 nm SiO2-NPs on viability and function of human bone marrow-derived MSCs (hMSCs); 2) to optimize a protocol of harmless hMSCs labelling and test its feasibility in a beating heart model.ResultsOptimal cell labelling is obtained after 16 h exposure of hMSCs to fluorescent 50 nm SiO2-NPs (50 µg mL−1); interestingly, lysosomal activation consequent to NPs storage is not associated to oxidative stress. During prolonged culture hMSCs do not undergo cyto- or genotoxicity, preserve their proliferative potential and their stemness/differentiation properties. Finally, the bright fluorescence emitted by internalized SiO2-NPs allows both clear visualization of hMSCs in normal and infarcted rat hearts and ultrastructural analysis of cell engraftment inside myocardial tissue.ConclusionsOverall, 50 nm SiO2-NPs display elevated compatibility with hMSCs in terms of lack of cyto- and genotoxicity and maintenance of important features of these cells. The demonstrated biosafety, combined with proper cell labelling and visualization in histological sections, make these SiO2-NPs optimal candidates for the purpose of stem cell tracking inside heart tissue.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-015-0141-1) contains supplementary material, which is available to authorized users.

The Current Dilemma and Breakthrough of Stem Cell Therapy in Ischemic Heart Disease

“…However, there are some disadvantages. For example, the division of stem cells will dilute the concentration of nanoparticles in the cells, which will affect the long-term observation effect, and cell death will cause the dispersion of nanoparticles (Gallina et al, 2015;Zhu et al, 2016). In general, the exogenous labeling method is simple and direct, but it has disadvantages such as low labeling efficiency, unstable labeling process, short duration of the label in the cell, and difficulty in tracking the whole process.…”

Experimental Strategies of Mesenchymal Stem Cell Propagation: Adverse Events and Potential Risk of Functional Changes

“…In the field of fluorescent labelling, there are some more examples of the negative influence of this kind of cell tagging on MSC biology. Gallina and coworkers reported that after fluorescent silica nanoparticle (SiO2-NP) MSC labelling, nanoparticles were accumulated in lysosomes and their number was substantially elevated compared to unlabelled cells [ 94 ]. Despite high number of lysosomes, neither oxidative stress nor cytotoxicity was noted.…”

Silica Nanoparticles Actively Engage With Mesenchymal Stem Cells in Improving Acute Functional Cardiac Integration

“…Up to now, however, there are only a few reports on the effects exerted on MSC functions by cellular uptake of different NP types [14,15], even though this would be of great interest for the design of high-performance NP-based imaging systems for regenerative medicine processes. We have developed a method of fluorescent staining with silica NPs (SiO 2 -NPs) suited to track hMSCs and validated this approach both in vitro [16,17] and ex vivo [18]. We already demonstrated that SiO 2 -NP uptake by hMSCs was well tolerated in the long term, did induce neither cell death nor genotoxic stress and did not alter proliferative activity and differentiation potential of hMSCs [16][17][18].…”