title: Hypoxia inducible factor-stabilizing bioactive glasses for directing mesenchymal stem cell behavior.
abstract: Oxygen tension is a known regulator of mesenchymal stem cell (MSC) plasticity, differentiation, proliferation, and recruitment to sites of injury. Materials capable of affecting the MSC oxygen-sensing pathway, independently of the environmental oxygen pressure, are therefore of immense interest to the tissue engineering (TE) and regenerative medicine community. In this study, we describe the evaluation of the effect of hypoxia inducible factor (HIF)-stabilizing bioactive glasses (BGs) on human MSCs. The dissolution products from these hypoxia-mimicking BGs stabilized HIF-1α in a concentration-dependent manner, altered cell proliferation and metabolism, and upregulated a number of genes involved in the hypoxic response (HIF1A, HIF2A, and VHL), MSC survival (SAG and BCL2), extracellular matrix remodeling (MMP1), and angiogenesis (VEGF and PDGF). These HIF-stabilizing materials can therefore be used to improve MSC survival and enhance regeneration in a number of TE strategies.
authors.affiliation: 1 Department of Materials, Imperial College London , London, United Kingdom .
authors.forename: Maria M
authors.initials: MM
authors.lastname: Azevedo
authors.forename: Olga
authors.initials: O
authors.lastname: Tsigkou
authors.forename: Rekha
authors.initials: R
authors.lastname: Nair
authors.forename: Julian R
authors.initials: JR
authors.lastname: Jones
authors.forename: Gavin
authors.initials: G
authors.lastname: Jell
authors.forename: Molly M
authors.initials: MM
authors.lastname: Stevens
mesh_terms: D015687:Cell Hypoxia; D002470:Cell Survival; D005786:Gene Expression Regulation; D005898:Glass / Q000737:chemistry*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D055550:Protein Stability; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A