Stepwise Differentiation of Mesenchymal Stem Cells Augments Tendon-Like Tissue Formation and Defect Repair In Vivo

Tendon injuries are common and present a clinical challenge, as they often respond poorly to treatment and result in long-term functional impairment. Inferior tendon healing responses are mainly attributed to insufficient or failed tenogenesis. The main objective of this study was to establish an efficient approach to induce tenogenesis of bone marrow-derived mesenchymal stem cells (BMSCs), which are the most common seed cells in tendon tissue engineering. First, representative reported tenogenic growth factors were used as media supplementation to induce BMSC differentiation, and the expression of teno-lineage transcription factors and matrix proteins was compared. We found that transforming growth factor (TGF)-β1 significantly induced teno-lineage-specific gene scleraxis expression and collagen production. TGF-β1 combined with connective tissue growth factor (CTGF) elevated tenomodulin and Egr1 expression at day 7. Hence, a stepwise tenogenic differentiation approach was established by first using TGF-β1 stimulation, followed by combination with CTGF for another 7 days. Gene expression analysis showed that this stepwise protocol initiated and maintained highly efficient tenogenesis of BMSCs. Finally, regarding in situ rat patellar tendon repair, tendons treated with induced tenogenic BMSCs had better structural and mechanical properties than those of the control group, as evidenced by histological scoring, collagen I and tenomodulin immunohistochemical staini...

Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Yin, Z., Guo, J., Wu, T.-y., Chen, X., Xu, L.-l., Lin, S.-e., Sun, Y.-x., Chan, K.-M., Ouyang, H., Li, G. Tags: Tissue Engineering and Regenerative Medicine, Mesenchymal Stem Cells Source Type: research