Mechanoactive Tenogenic Differentiation of Human Mesenchymal Stem Cells
- 1 October 2008
- journal article
- Published by Mary Ann Liebert Inc in Tissue Engineering, Part A
- Vol. 14 (10), 1615-1627
- https://doi.org/10.1089/ten.tea.2006.0415
Abstract
A mesenchymal stem cell (MSC)-seeded collagen gel under static or dynamic tension is a well-established model to study the potential of MSCs in regenerating a tendon- or ligament-like tissue. Using this model, upregulation of fibrillar collagen mRNA expression and protein production has been demonstrated in response to cyclic tensile mechanical stimulation. However, the mechanisms driving MSC tenogenesis (differentiation into tendon or ligament fibroblasts) have not been elucidated. This study investigated the mechanisms of tenogenesis of human bone marrow-derived MSCs in a dynamic, three-dimensional (3D) tissue-engineering model by investigating the effects of cyclic stretching on matrix production and gene expression of candidate tendon and ligament markers. The 3D MSC tenogenesis culture system upregulated scleraxis, but cyclic stretching was required to maintain expression of this putative tendon marker over time. Enhanced tendinous neo-tissue development demonstrated with extracellular matrix staining was largely due to changes in matrix deposition and remodeling activity under dynamic loading conditions, as evidenced by differential regulation of matrix metalloproteinases at a transcriptional level with minimal changes in collagen mRNA levels. Regulation of Wnt gene expression with cyclic stimulation suggested a similar role for Wnt4 versus Wnt5a in tenogenesis as in cartilage development. This first report of the potential involvement of matrix remodeling and Wnt signaling during tenogenesis of human MSCs in a dynamic, 3D tissue-engineering model provides insights into the mechanisms of tenogenesis in a mechanoactive environment and supports the therapeutic potential of adult stem cells.Keywords
This publication has 48 references indexed in Scilit:
- Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendonsDevelopment, 2007
- Functional Efficacy of Tendon Repair ProcessesAnnual Review of Biomedical Engineering, 2004
- Tissue Engineering of LigamentsAnnual Review of Biomedical Engineering, 2004
- Transdifferentiation potential of human mesenchymal stem cells derived from bone marrowThe FASEB Journal, 2004
- Physical exercise can influence local levels of matrix metalloproteinases and their inhibitors in tendon-related connective tissueJournal of Applied Physiology, 2004
- Tissue-Engineering Approach to the Repair and Regeneration of Tendons and LigamentsTissue Engineering, 2003
- Effect of Amplitude and Frequency of Cyclic Tensile Strain on the Inhibition of MMP-1 mRNA Expression in Tendon Cells: An In Vitro StudyConnective Tissue Research, 2003
- ATP modulates load‐inducible IL‐1β, COX 2, and MMP‐3 gene expression in human tendon cellsJournal of Cellular Biochemistry, 2003
- Comparative analysis of the expression and regulation of Wnt5a, Fz4, and Frzb1 during digit formation and in micromass culturesDevelopmental Dynamics, 2002
- Use of mesenchymal stem cells in a collagen matrix for achilles tendon repairJournal of Orthopaedic Research, 1998