Equine adult, fetal and ESC-tenocytes have differential migratory, proliferative and gene expression responses to factors upregulated in the injured tendon.
Authors: R. E. Beaumont, E. J. Smith, C. David, Yasmin Z. Paterson, Elena Faull, D. Guest
Journal: Cells & development
Summary
# Editorial Summary: Differential Tenocyte Responses to Injury-Associated Factors Tendon injuries in horses carry a frustratingly high re-injury rate, largely because adult tendon repair relies on scar tissue formation rather than true regeneration—a stark contrast to the scarless healing observed in fetal tendons, whose underlying mechanisms remain poorly understood. Researchers compared how adult, fetal, and embryonic stem cell-derived equine tenocytes responded to cytokines, chemokines and growth factors known to be elevated post-injury, using both two-dimensional migration and proliferation assays alongside three-dimensional wound closure models. Key findings revealed that fetal tenocytes occupy a biological middle ground: their proliferative responses align more closely with adult cells, whilst their migratory behaviour and three-dimensional wound healing capacity show characteristics intermediate to both adult and ESC-derived tenocytes. Notably, transforming growth factor-beta 3 (TGFβ3) enhanced wound closure in both adult and fetal cells, whereas fibroblast growth factor 2 (FGF2) significantly inhibited adult cell responses, suggesting these factors may be critical in determining whether an injury undergoes scarring repair or regenerative healing. These differential cellular responses offer a mechanistic framework for developing cell-based therapies—potentially guiding decisions about which cell populations to use in regenerative protocols and which growth factor combinations might shift the biological environment toward regeneration rather than fibrosis.
Read the full abstract on PubMed
Practical Takeaways
- •Future cell-based therapies targeting tendon regeneration may need to manipulate specific growth factor pathways (TGFβ3 promotion, FGF2 inhibition) to promote scarless healing rather than fibrotic repair
- •ESC-derived tenocytes behave distinctly from native adult tenocytes and may offer therapeutic advantages, but require further characterization before clinical application
- •Understanding why fetal tendons heal without scarring could inform treatment strategies to reprogram adult tendon responses toward regeneration rather than repair
Key Findings
- •Fetal and adult tenocytes show similar proliferative responses to injury-upregulated factors, but differ from ESC-derived tenocytes in 2D assays
- •Fetal tenocytes display intermediate migratory and wound-healing characteristics between adult and ESC-tenocytes in 3D models
- •TGFβ3 enhances 3D wound closure in both adult and fetal tenocytes, while FGF2 significantly inhibits adult tenocyte response
- •Differential cellular responses to post-injury cytokines and growth factors may determine whether tendon undergoes regeneration versus scar-tissue repair