title: On the use of dexamethasone-loaded liposomes to induce the osteogenic differentiation of human mesenchymal stem cells.
abstract: Stem cells have received considerable attention by the scientific community because of their potential for tissue engineering and regenerative medicine. The most frequently used method to promote their differentiation is supplementation of the in vitro culture medium with growth/differentiation factors (GDFs). The limitations of that strategy caused by the short half-life of GDFs limit its efficacy in vivo and consequently its clinical use. Thus, the development of new concepts that enable the bioactivity and bioavailability of GDFs to be protected, both in vitro and in vivo, is very relevant. Nanoparticle-based drug delivery systems can be injected, protect the GDFs and enable spatiotemporal release kinetics to be controlled. Liposomes are well-established nanodelivery devices presenting significant advantages, viz. a high load-carrying capacity, relative safety and easy production, and a versatile nature in terms of possible formulations and surface functionalization. The main objective of the present study was to optimize the formulation of liposomes to encapsulate dexamethasone (Dex). Our results showed that the optimized Dex-loaded liposomes do not have any cytotoxic effect on human bone marrow-derived mesenchymal stem cells (hBMSCs). More importantly, they were able to promote an earlier induction of differentiation of hBMSCs into the osteogenic lineage, as demonstrated by the expression of osteoblastic markers, both phenotypically and genotypically. We concluded that Dex-loaded liposomes represent a viable nanoparticle strategy with enhanced safety and efficacy for tissue engineering and regenerative medicine.
authors.affiliation: 3Bs Research Group - Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909, Caldas das Taipas, Guimarães, Portugal.|ICVS/3Bs, PT Government Associated Laboratory, Braga, Guimarães, Portugal.
authors.forename: Nelson
authors.initials: N
authors.lastname: Monteiro
authors.affiliation: 3Bs Research Group - Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909, Caldas das Taipas, Guimarães, Portugal.|ICVS/3Bs, PT Government Associated Laboratory, Braga, Guimarães, Portugal.
authors.forename: Albino
authors.initials: A
authors.lastname: Martins
authors.affiliation: 3Bs Research Group - Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909, Caldas das Taipas, Guimarães, Portugal.|ICVS/3Bs, PT Government Associated Laboratory, Braga, Guimarães, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Ribeiro
authors.affiliation: Research Centre Officina Mathematical, Department of Mathematics for Science and Technology, University of Minho, Campus de Azurém, 4800-058, Guimarães, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Faria
authors.affiliation: Centre for Neurosciences and Cell Biology (CNC), Faculty of Pharmacy of the University of Coimbra (FFUC), 3000, Coimbra, Portugal.
authors.forename: Nuno A
authors.initials: NA
authors.lastname: Fonseca
authors.affiliation: Centre for Neurosciences and Cell Biology (CNC), Faculty of Pharmacy of the University of Coimbra (FFUC), 3000, Coimbra, Portugal.
authors.forename: João N
authors.initials: JN
authors.lastname: Moreira
authors.affiliation: 3Bs Research Group - Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909, Caldas das Taipas, Guimarães, Portugal.|ICVS/3Bs, PT Government Associated Laboratory, Braga, Guimarães, Portugal.
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
authors.affiliation: 3Bs Research Group - Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909, Caldas das Taipas, Guimarães, Portugal.|ICVS/3Bs, PT Government Associated Laboratory, Braga, Guimarães, Portugal.
authors.forename: Nuno M
authors.initials: NM
authors.lastname: Neves
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology* / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008081:Liposomes; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D017348:Microscopy, Electron, Scanning Transmission; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D008081:Liposomes; D003907:Dexamethasone; D000469:Alkaline Phosphatase
keywords: bioactive agent; delivery system; dexamethasone; liposome; nanoparticle; stem cell differentiation