ArticleMatrix biology : journal of the International Society for Matrix Biology2010
Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 74 citations in OpenAlex.
- Single-cell transcriptomics reveals that tenocyte-derived MIF contributes to tendon injury pathogenesis.iScience · 2026Article
- Human adipose stromal cells differentiate towards a tendon phenotype with adapted visco-elastic properties in a 3D-culture system.Biology open · 2025Article
- Active synthesis of type I collagen homotrimer in Dupuytren's fibrosis is unaffected by anti-TNF-α treatment.JCI insight · 2025Article
- Fibrin Scaffolds Perfused with Transforming Growth Factor-β1 as an In Vitro Model to Study Healthy and Tendinopathic Human Tendon Stem/Progenitor Cells.International journal of molecular sciences · 2024Article
- Recent Advances in the Use of Stem Cells in Tissue Engineering and Adjunct Therapies for Tendon Reconstruction and Future Perspectives.International journal of molecular sciences · 2024Review
- Cell-Based Therapies for Rotator Cuff Injuries: An Updated Review of the Literature.International journal of molecular sciences · 2024Review
- A preliminary study into the emergence of tendon microstructure during postnatal development.Matrix biology plus · 2024Article
- Biological and Mechanical Factors and Epigenetic Regulation Involved in Tendon Healing.Stem cells international · 2023Review
- Tendon-Specific Activation of Tenogenic Transcription Factors Enables Keeping Tenocytes' Identity In Vitro.International journal of molecular sciences · 2022Article
- Autophagy guards tendon homeostasis.Cell death & disease · 2022Article
- CTRP3 exacerbates tendinopathy by dysregulating tendon stem cell differentiation and altering extracellular matrix composition.Science advances · 2021Article
- A Tendon-Specific Double Reporter Transgenic Mouse Enables Tracking Cell Lineage and Functions Alteration In Vitro and In Vivo.International journal of molecular sciences · 2021Article
- Growth factor and macromolecular crowding supplementation in human tenocyte culture.Biomaterials and biosystems · 2021Article
- Comparative Analysis of Tenogenic Gene Expression in Tenocyte-Derived Induced Pluripotent Stem Cells and Bone Marrow-Derived Mesenchymal Stem Cells in Response to Biochemical and Biomechanical Stimuli.Stem cells international · 2021Article
- A brief history of tendon and ligament bioreactors: Impact and future prospects.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Review
- Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro.BMC musculoskeletal disorders · 2020Article
- In Vitro Innovation of Tendon Tissue Engineering Strategies.International journal of molecular sciences · 2020Review
- Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes.Stem cell research & therapy · 2020Article
- TGF-β3 Loaded Electrospun Polycaprolacton Fibre Scaffolds for Rotator Cuff Tear Repair: An in Vivo Study in Rats.International journal of molecular sciences · 2020Article
- Mechanical and molecular parameters that influence the tendon differentiation potential of C3H10T1/2 cells in 2D- and 3D-culture systems.Biology open · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tendon-like tissue generated from stem cells in vitro has the potential to replace tendons and ligaments lost through injury and disease. However, thus far, no information has been available on the mechanism of tendon formation in vitro and how to accelerate the process. We show here that human mesenchymal stem cells (MSCs) and bone marrow-derived mononuclear cells (BM-MNCs) can generate tendon-like tissue in 7days mediated by transforming growth factor (TGF) β3. MSCs cultured in fixed-length fibrin gels spontaneously synthesized narrow-diameter collagen fibrils and exhibited fibripositors (actin-rich, collagen fibril-containing plasma membrane protrusions) identical to those that occur in embryonic tendon. In contrast, BM-MNCs did not synthesize tendon-like tissue under these conditions. We performed real-time PCR analysis of MSCs and BM-MNCs. MSCs upregulated genes encoding type I collagen, TGFβ3, and Smad2 at the time of maximum contraction of the tendon-like tissue (7days). Western blot analysis showed phosphorylation of Smad2 at maximum contraction. The TGFβ inhibitor SB-431542, blocked the phosphorylation of Smad2 and stopped the formation of tendon-like tissue. Quantitative PCR showed that BM-MNCs expressed very low levels of TGFβ3 compared to MSCs. Therefore we added exogenous TGFβ3 protein to BM-MNCs in fibrin gels, which resulted in phosphorylation of Smad2, synthesis of collagen fibrils, the appearance of fibripositors at the plasma membrane, and the formation of tendon-like tissue. In conclusion, MSCs that self-generate TGFβ signaling or the addition of TGFβ3 protein to BM-MNCs in fixed-length fibrin gels spontaneously make embryonic tendon-like tissue in vitro within 7days.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.