title: Short bouts of mechanical loading are as effective as dexamethasone at inducing matrix production by human bone marrow mesenchymal stem cell.
abstract: Dexamethasone (Dex) is used widely to induce differentiation in human mesenchymal stem cells (hMSCs); however, using a pharmaceutical agent to stimulate hMSC differentiation is not the best choice for engineered tissue transplantation due to potential side-effects. The goal of the present study was to investigate the effects of dynamic compressive loading on differentiation and mineralized matrix production of hMSCs in 3D polyurethane scaffolds, using a loading regimen previously shown to stimulate mineralised matrix production of mature bone cells (MLO-A5). hMSCs were seeded in polyurethane scaffolds and cultured in standard culture media with or without Dex. Cell-seeded scaffolds were compressed at 5% global strain for 2 h on day 9 and then every 5 days in a media-filled sterile chamber. Samples were tested for mRNA expression of alkaline phosphatase (ALP), osteopontin (OPN), collagen type 1 (col 1) and runt-related transcription factor-2 (RUNX-212 h) after the first loading, cell viability by MTS assay and alkaline phosphatase activity at day 12 of culture and cell viability, collagen content by Sirius red and calcium content by alizarin red at day 24 of culture. Neither Dex nor loading had significant effects on cell viability. Collagen content was significantly higher (p<0.01) in the loaded group compared with the non-loaded group in all conditions. There was no difference in ALP activity or the amount of collagen and calcium produced between the non-loaded group supplemented with Dex and the loaded group without Dex. We conclude that dynamic loading has the ability to stimulate osteogenic differentiation of hMSC in the absence of glucocorticoids.
authors.affiliation: Department of Materials Science and Engineering, Kroto Research Institute, Broad Lane, University of Sheffield, Sheffield S3 7HQ, UK.
authors.forename: A
authors.initials: A
authors.lastname: Sittichokechaiwut
authors.forename: J H
authors.initials: JH
authors.lastname: Edwards
authors.forename: A M
authors.initials: AM
authors.lastname: Scutt
authors.forename: G C
authors.initials: GC
authors.lastname: Reilly
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D050657:Core Binding Factor alpha Subunits / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D055595:Mechanical Phenomena; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D023822:Tissue Engineering
chemical_list: D024042:Collagen Type I; D050657:Core Binding Factor alpha Subunits; D005938:Glucocorticoids; D012333:RNA, Messenger; D053495:Osteopontin; D003907:Dexamethasone; D000469:Alkaline Phosphatase