title: Osteogenic predifferentiation of human bone marrow-derived stem cells by short-term mechanical stimulation.
abstract: It is commonly accepted that bone marrow-derived stem cells (BMSCs) have to be expanded in vitro, but a prolonged time in culture decreases their multilineage potential. Mechanical and biological stimuli have been used to improve their osteogenic potential. While long-term stimulation has been shown to improve osteogenic differentiation, it remains to be seen whether short-term stimulation is also sufficient.We investigated the influence of 24 hours' cyclic loading (0.05Hz, 4kPa) on gene expression of human BMSCs in three-dimensional fibrin-DMEM constructs (n=7) in a compression bioreactor using DNA-array technology. Expression of the following genes showed a significant increase after mechanical stimulation: 2.6-fold osteopontin (OPN) and integrin-β1 (ITGB1), 2.2-fold transforming growth factor-β-receptor 1 (TGF-β-R1) and 2.4-fold SMAD5 expression, compared to controls without mechanical stimulation (p<0.05 each). Platelet-derived growth factor-α (PDGF-α ) and annexin-V were also significantly overexpressed, the mechanical stimulation resulting in a 1.8-fold and 1.6-fold expression (p<0.05).Cells were identified as osteoblast precursors with a high proliferative capacity. Given the identical in-vitro environment for both groups, the increase in gene expression has been interpreted as a direct influence of cyclic mechanical stimulation on osteogenic differentiation. It may be postulated that short-term mechanical stimulation results in an improved osseous integration of tissue engineered grafts in bone defect healing.
authors.affiliation: Orthopaedic Department, Center for Musculoskeletal Surgery.
authors.forename: Doerte
authors.initials: D
authors.lastname: Matziolis
authors.forename: Jens
authors.initials: J
authors.lastname: Tuischer
authors.forename: Georg
authors.initials: G
authors.lastname: Matziolis
authors.forename: Grit
authors.initials: G
authors.lastname: Kasper
authors.forename: Georg
authors.initials: G
authors.lastname: Duda
authors.forename: Carsten
authors.initials: C
authors.lastname: Perka