RESEARCH ARTICLE


Osteogenic Predifferentiation of Human Bone Marrow-Derived Stem Cells by Short-Term Mechanical Stimulation



Doerte Matziolis*, 1, Jens Tuischer 1, Georg Matziolis 1, Grit Kasper 2, Georg Duda 2, Carsten Perka 1
1 Orthopaedic Department, Center for Musculoskeletal Surgery
2 Julius Wolff Institute, Charité, University Medicine Berlin, Germany


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Creative Commons License
© Matziolis et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Orthopaedic Department, Center for Musculoskeletal Surgery, Charité - University Medicine Berlin, Charitéplatz 1, D-10117 Berlin, Germany; Tel: 0049 - 30 - 450652206; Fax: 0049 - 30 - 450515909; E-mail: doerte.matziolis@charite.de


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.

Keywords: Osteogenic predifferentiation, human bone marrow-derived stem cells, mechanical stimulation, bioreactor.