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Chondrogenesis of human bone marrow-derived mesenchymal stem cells is modulated by complex mechanical stimulation and adenoviral-mediated overexpression of bone morphogenetic protein 2

Neumann, Alexander J., Alini, Mauro, Archer, Charles William and Stoddart, Martin J. 2013. Chondrogenesis of human bone marrow-derived mesenchymal stem cells is modulated by complex mechanical stimulation and adenoviral-mediated overexpression of bone morphogenetic protein 2. Tissue Engineering Part A 19 (11-12) , pp. 1285-1294. 10.1089/ten.tea.2012.0411

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Abstract

Currently available methods to treat articular cartilage defects still fail to demonstrate satisfactory outcomes for many patients. Functional tissue engineering using human bone marrow-derived mesenchymal stem cells (hMSCs) is a promising alternative approach for the treatment of these defects. This study strived to investigate the combined effect of complex mechanical stimulation and adenoviral-mediated overexpression of bone morphogenetic protein 2 (BMP-2) on hMSC chondrogenesis. hMSCs were encapsulated in a fibrin hydrogel and seeded into biodegradable polyurethane (PU) scaffolds. A novel three-dimensional transduction protocol was used to transduce cells with an adenovirus encoding for BMP-2 (Ad.BMP-2). Control cells were left untransduced. Cells were cultured for 7 or 28 days in a chondropermessive medium, which lacks any exogenous growth factors. Thereby, the in vivo situation is mimicked more precisely. hMSCs in fibrin-PU composite scaffolds were either left as free-swelling controls or mechanically stimulated using a custom-built bioreactor system that is able to generate joint-like forces. Outcome parameters measured were BMP-2 concentration within the culture medium, and biochemical and gene expression analysis. Mechanical stimulation resulted in an upregulation of chondrogenic genes. Further, glycosaminoglycan (GAG)/DNA ratios were elevated in mechanically stimulated groups. Transduction with Ad.BMP-2 led to a pronounced upregulation of the gene aggrecan and an upregulation of Sox9 message after 7 days. Furthermore, a synergistic effect in combination with mechanical stimulation on collagen 2 message was detected after 7 days. This synergistic increase was more than 8-fold if compared to the additive effect of the application of each stimulus on its own. However, BMP-2 overexpression consistently resulted in a trend toward decreased GAG/DNA ratios in both mechanical stimulated and unloaded groups.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH426 Genetics
Publisher: Mary Ann Liebert
ISSN: 1937-3341
Last Modified: 19 Mar 2016 23:35
URI: http://orca.cf.ac.uk/id/eprint/57334

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