Mesenchymal stem cell secretome improves tendon cell viability in vitro and tendon-bone healing in vivo when a tissue engineering strategy is used in a rat model of chronic massive rotator cuff tear

Abstract

BACKGROUND: Massive rotator cuff tears (MRCTs) represent a major clinical concern, especially when degeneration and chronicity are involved, which highly compromise healing capacity.

PURPOSE: To study the effect of the secretome of mesenchymal stem cells (MSCs) on tendon cells (TCs) followed by the combination of these activated TCs with an electrospun keratin-based scaffold to develop a tissue engineering strategy to improve tendon-bone interface (TBi) healing in a chronic MRCT rat model.

STUDY DESIGN: Controlled laboratory study.

METHODS: Human TCs (hTCs) cultured with the human MSCs (hMSCs) secretome (as conditioned media [CM]) were combined with keratin electrospun scaffolds and further implanted in a chronic MRCT rat model. Wistar-Han rats (N = 15) were randomly assigned to 1 of 3 groups: untreated lesion (MRCT group, n = 5), lesion treated with a scaffold only (scaffold-only group, n = 5), and lesion treated with a scaffold seeded with hTCs preconditioned with hMSCs-CM (STC_hMSC_CM group, n = 5). After sacrifice, 16 weeks after surgery, the rotator cuff TBi was harvested for histological analysis and biomechanical testing.

RESULTS: The hMSCs secretome increased hTCs viability and density in vitro. In vivo, a significant improvement of the tendon maturing score was observed in the STC_hMSC_CM group (mean ± standard error of the mean, 15.6 ± 1.08) compared with the MRCT group (11.0 ± 1.38; P < .05). Biomechanical tests revealed a significant increase in the total elongation to rupture (STC_hMSC_CM, 11.99 ± 3.30 mm; scaffold-only, 9.89 ± 3.47 mm; MRCT, 5.86 ± 3.16 mm; P < .05) as well as a lower stiffness (STC_hMSC_CM, 6.25 ± 1.74 N/mm; scaffold-only, 6.72 ± 1.28 N/mm; MRCT, 11.54 ± 2.99 N/mm; P < .01).

CONCLUSION: The results demonstrated that hMSCs-CM increased hTCs viability and density in vitro. Clear benefits also were observed when these primed cells were integrated into a tissue engineering strategy with an electrospun keratin scaffold, as evidenced by improved histological and biomechanical properties for the STC_hMSC_CM group compared with the MRCT group.

CLINICAL RELEVANCE: This work supports further investigation into the use of MSC secretome for priming TCs toward a more differentiated phenotype, and it promotes the tissue engineering strategy as a promising modality to help improve treatment outcomes for chronic MRCTs.