Fibrin Scaffolds Perfused with Transforming Growth Factor-β1 as an In Vitro Model to Study Healthy and Tendinopathic Human Tendon Stem/Progenitor Cells.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Tendons*/cytology ; Tendons*/metabolism ; Tissue Scaffolds*/chemistry ; Stem Cells*/metabolism ; Stem Cells*/cytology ; Fibrin*/metabolism ; Transforming Growth Factor beta1*/metabolism ; Collagen Type I*/metabolism ; Collagen Type I*/genetics; Humans ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Tendinopathy/metabolism ; Tendinopathy/pathology ; Cells, Cultured ; Collagen Type III/metabolism ; Collagen Type III/genetics ; Collagen Type I, alpha 1 Chain/metabolism ; Middle Aged ; Male ; Cell Survival/drug effects ; Tissue Engineering/methods ; Membrane Proteins
    • Abstract:
      A limited understanding of tendon cell biology in healthy and pathological conditions has impeded the development of effective treatments, necessitating in vitro biomimetic models for studying tendon events. We established a dynamic culture using fibrin scaffolds, bioengineered with tendon stem/progenitor cells ( h TSPCs) from healthy or diseased human biopsies and perfused with 20 ng/mL of human transforming growth factor-β1 for 21 days. Both cell types showed long-term viability and upregulated Scleraxis (SCX-A) and Tenomodulin (TNMD) gene expressions, indicating tenogenic activity. However, diseased h TSPCs underexpressed collagen type I and III (COL1A1 and COL3A1) genes and exhibited lower SCX-A and TNMD protein levels, but increased type I collagen production, with a type I/type III collagen ratio > 1.5 by day 14, matching healthy cells. Diseased h TSPCs also showed constant high levels of pro-inflammatory cytokines, such as IL-8 and IL-6. This biomimetic environment is a valuable tool for studying tenogenic and inflammatory events in healthy and diseased tendon cells and identifying new therapeutic targets.
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    • Grant Information:
      955685 European Union's Horizon 2020 Research and Innovation Program under Marie Skłodowska-Curie Actions
    • Contributed Indexing:
      Keywords: 3D advanced in vitro model; cytokines; dynamic culture; human tendon/stem progenitor cells; human transforming growth factor-β1; perfusion; tenogenesis; tissue engineering
    • Accession Number:
      9001-31-4 (Fibrin)
      0 (Transforming Growth Factor beta1)
      0 (SCX protein, human)
      0 (Collagen Type I)
      0 (Basic Helix-Loop-Helix Transcription Factors)
      0 (TNMD protein, human)
      0 (Collagen Type III)
      0 (COL3A1 protein, human)
      0 (Collagen Type I, alpha 1 Chain)
      0 (COL1A1 protein, human)
      0 (Membrane Proteins)
    • Publication Date:
      Date Created: 20240914 Date Completed: 20240914 Latest Revision: 20240916
    • Publication Date:
      20240916
    • Accession Number:
      PMC11395617
    • Accession Number:
      10.3390/ijms25179563
    • Accession Number:
      39273510