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      Cross-Talk Between Human Tenocytes and Bone Marrow Stromal Cells Potentiates Extracellular Matrix Remodeling In Vitro.

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          Abstract

          Tendon and ligament (T/L) pathologies account for a significant portion of musculoskeletal injuries and disorders. Tissue engineering has emerged as a promising solution in the regeneration of both tissues. Specifically, the use of multipotent human mesenchymal stromal cells (hMSC) has shown great promise to serve as both a suitable cell source for tenogenic regeneration and a source of trophic factors to induce tenogenesis. Using four donor sets, we investigated the bidirectional paracrine tenogenic response between human hamstring tenocytes (hHT) and bone marrow-derived hMSC. Cell metabolic assays showed that only one hHT donor experienced sustained notable increases in cell metabolic activity during co-culture. Histological staining confirmed that co-culture induced elevated collagen protein levels in both cell types at varying time-points in two of four donor sets assessed. Gene expression analysis using qPCR showed the varied up-regulation of anabolic and catabolic markers involved in extracellular matrix maintenance for hMSC and hHT. Furthermore, analysis of hMSC/hHT co-culture secretome using a reporter cell line for TGF-β, a potent inducer of tenogenesis, revealed a trend of higher TGF-β bioactivity in hMSC secretome compared to hHT. Finally, hHT cytoskeletal immunostaining confirmed that both cell types released soluble factors capable of inducing favorable tenogenic morphology, comparable to control levels of soluble TGF-β1. These results suggest a potential for TGF-β-mediated signaling mechanism that is involved during the paracrine interplay between the two cell types that is reminiscent of T/L matrix remodeling/turnover. These findings have significant implications in the clinical use of hMSC for common T/L pathologies.

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          Author and article information

          Journal
          J. Cell. Biochem.
          Journal of cellular biochemistry
          Wiley-Blackwell
          1097-4644
          0730-2312
          Mar 2016
          : 117
          : 3
          Affiliations
          [1 ] Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey.
          [2 ] MIRA Institute for Biomedical Technology and Technical Medicine, Department of Tissue Regeneration, University of Twente, Enschede, The Netherlands.
          [3 ] Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.
          [4 ] CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
          [5 ] UC-Biotech-Cantanhede, Cantanhede, Portugal.
          Article
          NIHMS790306
          10.1002/jcb.25353
          4943840
          26308651
          baaa8b2f-e414-4446-805d-8ecdda8b946a
          History

          TRANSFORMING GROWTH FACTOR BETA,CO-CULTURE,LIGAMENT,TENDON,PARACRINE SIGNALING,MESENCHYMAL STROMAL CELLS

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