Human mesenchymal stem cells differentiate into an osteogenic lineage in presence of strontium containing bioactive glass nanoparticles
File(s)
Author(s)
Parichart, Naruphontjirakul
Tsigkou, Olga
Li, Siwei
Porter, Alexandra
Jones, Julian
Type
Journal Article
Abstract
While bioactive glass and ions released during its dissolution are known to stimulate osteoblast cells, the effect bioactive glass has on human stem cells is not clear. Here, we show that spherical monodispersed strontium containing bioactive nanoparticles (Sr-BGNPs) of composition 90.6 mol% SiO2, 5.0 mol% CaO, 4.4% mol% SrO (4.4%Sr-BGNPs) and 88.8 mol% SiO2, 1.8 mol% CaO, and 9.4 mol% SrO (9.4%Sr-BGNPs) stimulate bone marrow derived human stem cell (hMSC) differentiation down an osteogenic pathway without osteogenic supplements. The particles were synthesised using a modified Stӧber process and had diameters of 90 ± 10 nm. Previous work on similar particles that did not contain Sr (80 mol% SiO2, 20 mol% CaO) showed stem cells did not differentiate when exposed to the particles. Here, both compositions of the Sr-BGNPs (up to concentration of 250 μg/mL) stimulated the early-, mid-, and late-stage markers of osteogenic differentiation and accelerated mineralisation in the absence of osteogenic supplements. Sr ions play a key role in osteogenic stem cell differentiation. Sr-BGNP dissolution products did not adversely affect hMSC viability and no significant differences in viability were measured between each particle composition. Confocal and transmission electron microscopy (TEM) demonstrated that monodispersed Sr- BGNPs were internalised and localised within vesicles in the cytoplasm of hMSCs. Degradation of particles inside the cells was observed, whilst maintaining effective cations (Ca and Sr) in their silica network after 24 h in culture. The uptake of Sr-BGNPs by hMSCs was reduced by inhibitors of specific routes of endocytosis, indicating that the Sr-BGNPs uptake by hMSCs was probably via mixed endocytosis mechanisms. Sr-BGNPs have potential as injectable therapeutic devices for bone regeneration or treatment of conditions such as osteoporosis, because of their ability deliver a sustained release of osteogenic inorganic cations, e.g. calcium (Ca) or and strontium (Sr), through particle degradation locally to cells.
Date Issued
2019-05-01
Date Acceptance
2019-03-20
Citation
Acta Biomaterialia, 2019, 90 (1), pp.373-392
ISSN
1742-7061
Publisher
Elsevier
Start Page
373
End Page
392
Journal / Book Title
Acta Biomaterialia
Volume
90
Issue
1
Copyright Statement
This paper is embargoed until 12 months after publication.
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Identifier
https://www.sciencedirect.com/science/article/pii/S1742706119302132
Grant Number
EP/M004414/1
Subjects
Science & Technology
Technology
Engineering, Biomedical
Materials Science, Biomaterials
Engineering
Materials Science
Bioactive glass
Bone marrow derived human stem cells
Nanoparticles
Strontium
Osteogenic
MESOPOROUS SILICA NANOPARTICLES
TRANSCRIPTION FACTOR OSTERIX
TERM BISPHOSPHONATE THERAPY
BONE-MARROW
IN-VITRO
OSTEOBLAST DIFFERENTIATION
GENE-EXPRESSION
45S5 BIOGLASS(R)
CELLULAR UPTAKE
IONIC PRODUCTS
Bioactive glass
Bone marrow derived human stem cells
Nanoparticles
Osteogenic
Strontium
Cell Differentiation
Cell Line
Glass
Humans
Mesenchymal Stem Cells
Nanoparticles
Osteogenesis
Strontium
Cell Line
Mesenchymal Stem Cells
Humans
Strontium
Glass
Cell Differentiation
Osteogenesis
Nanoparticles
Biomedical Engineering
Publication Status
Published
Date Publish Online
2019-03-23