Bone Marrow Stem Cells Augmented with Tendon Tissue Lysate Promote Enhanced Achilles Tendon Healing

INTRODUCTION/OBJECTIVE: Tendon injuries, particularly of the Achilles tendon, are common in both athletic and aging populations. Conventional repair strategies often result in suboptimal healing due to the inherent avascularity and limited regenerative potential of tendon tissue. For tendon regeneration, stem cells have become a promising treatment option. Preconditioning Bone Marrow- Derived Stem Cells (BMSCs) with Tendon Tissue Lysate (TTL), a heterogeneous tissue-derived preparation, may influence tenogenic differentiation. The objective of the study was to evaluate the effect of tendon tissue lysate preconditioning on Bone Marrow-Derived Stem Cells (BMSCs) viability and tenogenic biomarker expression in a rat model of Achilles tendon injury. METHODS: Both in vitro and in vivo evaluations were performed. Bone Marrow-Derived Stem Cells (BMSCs) were isolated from rats, cultured, and treated with Tendon Tissue Lysate (TTL). Cell viability was assessed using MTT, crystal violet, and trypan blue assays. Tenogenic differentiation was evaluated via ELISA for Tenomodulin and TGF-β1. For in vivo assessment, forty Sprague-Dawley rats were randomly divided into four groups (n=10/group): (1) healthy control, (2) tendon injury only, (3) injury treated with BMSCs, and (4) tendon injury treated with BMSCs preconditioned with TTL. Achilles tendon injury was induced in groups 2-4, followed by treatments via direct injection into the injury site in groups 3 and 4, except group 2. Serum biomarkers (CRP, IL-6, TGF-β1, TNMD) were quantified, and further tendon healing was evaluated histologically. RESULTS: TTL did not significantly affect viability. Morphology and ELISA indicated a favorable tenogenic response at 100 μg/mL. In vivo, rats treated with TTL-preconditioned BMSCs demonstrated more organized tendon histology, increased TNMD and TGF-β1 levels, and reduced CRP and IL-6 compared to other groups. DISCUSSION: The results suggest that Tendon Tissue Lysate (TTL) may support tenogenic differentiation of BMSCs. TTL may provide an optimum microenvironment that supports tendon repair. Increased levels of TNMD and TGF-β1 are consistent with tendon maturation and extracellular remodeling. Histological analysis shows improvement in collagen alignment. CONCLUSION: Overall, preconditioning of BMSCs with tendon tissue lysate was associated with favorable tenogenic, inflammatory, and histological changes related to tendon repair. TTL represents a promising biological adjunct for optimizing stem cell-based therapies in tendon tissue engineering.