Effects of Conditioned Media From Human Umbilical Cord-Derived Mesenchymal Stem Cells on Tenocytes From Degenerative Rotator Cuff Tears in an Interleukin 1β-Induced Tendinopathic Condition.

Background: Evidence suggests that mesenchymal stem cells (MSCs) are safe for treating different tendinopathies. Synovial fluid is a pooled environment of biomarkers from the inflammatory and degenerative joint cavity. Understanding the effects of synovial fluid on MSCs is important, as it is the first microenvironment that administered MSCs encounter. Several studies have reported that exposure to osteoarthritic synovial fluid-activated MSCs increased the release of soluble factors; however, the paracrine effects of shoulder synovial fluid-stimulated umbilical cord-derived MSCs (SF-UC-MSCs) on tendinopathy have yet to be investigated.

Purpose: To assess the effects of the conditioned media from SF-UC-MSCs on tenocytes from degenerative rotator cuff tears in an interleukin-1β (IL-1β)-induced tendinopathic condition.

Study Design: Controlled laboratory study.

Methods: UC-MSCs were isolated and cultured from healthy, full-term deliveries by cesarean section. Tenocytes were isolated and cultured from patients with degenerative rotator cuff tears. Conditioned media were obtained from UC-MSCs stimulated with synovial fluid. To evaluate the gene expression of proinflammatory and anti-inflammatory cytokines, enzymes and their inhibitors, matrix molecules, and growth factors, the tenocytes were cultured with IL-1β and 50% of the conditioned media from the SF-UC-MSCs; quantitative, real-time, reverse transcriptase polymerase chain reaction was also performed. A prostaglandin E2 (PGE2) assay was performed to investigate the PGE2 level secreted by the tenocytes. Western blotting was performed to examine protein synthesis of collagen type I and III. Cell viability, senescence, and apoptosis assays were also performed.

Results: The conditioned media from the SF-UC-MSCs interfered with the inflammatory gene expression on tenocytes induced by IL-1β, but it increased the gene expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3. Meanwhile, the conditioned media decreased the PGE2 level on cells induced by IL-1β. It did increase the type I/III ratio of gene expression and protein synthesis, mainly through the induction of type I collagen. Conditioned media of SF-UC-MSCs reversed senescence and apoptosis induced by IL-1β.

Conclusion: Study findings indicated that the conditioned media from SF-UC-MSCs had anti-inflammatory effects and cytoprotective effects on IL-1β-treated tenocytes from degenerative rotator cuff tears.

Clinical Relevance: UC-MSCs have useful potential for the treatment of tendinopathy in practice.