Tendon-derived stem cells undergo spontaneous tenogenic differentiation

• TDSCs had the potential of spontaneous tenogenic differentiation.
• The tenogenic transcription factors were upregulated during this process.
• The expression of ECM and other tendon markers was promoted during this process.
• The collagen synthesis ability was also increased during this process.

Tendon-derived stem cell (TDSC) is a subpopulation of residing stem cells within the intact tendon tissues, with the capacities of self-renewal, clonogenicity, and three-lineage differentiation. Compared with bone marrow derived mesenchymal stem cells (BMSCs), TDSCs are superior for tendon injuries repair as they remain some tendon tissue-specific differentiation properties. In the present study, TDSC was found to undergo spontaneous tenogenic differentiation in which the expression of tenogenic markers were increased while the expression of stemness markers decreased with time in TDSCs culture (without tenogenic induction medium). The further collagen synthesis ability was correspondingly increased during this process. After a longer period of culture, the monolayer of TDSCs formed a “3D” layers with rich extracellular matrices of typical tendon tissues. In addition, the key tenogenic transcription factors, such as Scx, Mkx, Egr1 and Eya1 were all up-regulated in this process. Finally, we compared the spontaneous tenogenic differentiation with TGF-β1-induced tenogenic differentiation of TDSCs, and the results showed that the spontaneous tenogenic differentiation of TDSCs was general character of TDSCs, similar to but weaker than the effect of TDSCs under tenogenic induction. Taken together, the present study identified that TDSCs had the potential of spontaneous tenogenic differentiation, which may be a better cell source for the treatment of tendon injury.