Tenogenic Cues Are Biochemically and Environmentally Distinct for Tendon Stem Cells and Mesenchymal/Stromal Stem Cells

Tendon injuries make up a large part of musculoskeletal issues worldwide. These injuries often do not heal fully because tendon tissues have a limited ability to regenerate. This study by Citro et al. looks at how different biochemical and environmental signals affect tenogenic differentiation in two important types of stem cells: mesenchymal/stromal stem cells (MSCs) and tendon-derived stem cells (TSCs).

The researchers on this paper examined the effects of three growth differentiation factors—GDF-5, GDF-6, and GDF-7—at different oxygen levels (normoxia at 21% O₂ compared to physoxia at 2% O₂). They analyzed gene expression of tenogenic markers like Scleraxis (Scx) and Tenomodulin (Tnmd), along with protein expression, to assess how well the cells developed into tenocyte-like cells.

Key findings include:

• GDF-7 was the most effective at promoting tenogenic differentiation in MSCs, especially in normoxic conditions.
• In contrast, TSCs naturally started tenogenic pathways in low oxygen (physoxic) conditions without the need for additional growth factors.
• The study highlights that MSCs and TSCs need different combinations of growth factors and oxygen levels to effectively turn into tendon-like cells.
• This work not only clarifies the different needs for tendon regeneration using stem cells but also helps design more focused tissue engineering strategies for treating tendinopathies.