Diclofenac and triamcinolone acetonide impair tenocytic differentiation and promote adipocytic differentiation of mesenchymal stem cells.

BACKGROUND: Tendinopathies are often empirically treated with oral/topical nonsteroidal anti-inflammatory medications and corticosteroid injections despite their unclear effects on tendon regeneration. Recent studies indicate that tendon progenitors exhibit stem cell-like properties, i.e., differentiation to osteoblasts, adipocytes, and chondrocytes, in addition to tenocytes. Our present study aims at understanding the effects of triamcinolone acetonide and diclofenac on tenocytic differentiation of mesenchymal stem cells. METHODS: The murine fibroblast C3H10T1/2 cell line was induced to tenocytic differentiation by growth differentiation factor-7. Cell proliferation and differentiation with the exposure of different concentrations of triamcinolone acetonide and diclofenac were measured by WST-1 assay and real-time polymerase chain reaction analysis, respectively. RESULTS: Cell proliferation was decreased in a concentration-dependent manner when exposed to triamcinolone acetonide and diclofenac. In addition to tenocytic differentiation, adipocyte formation was observed, both at gene expression and microscopic level, when the cells were exposed to triamcinolone acetonide or high concentrations of diclofenac. CONCLUSIONS: Our results indicate that triamcinolone acetonide and diclofenac might alter mesenchymal stem cell differentiation in a nonfavorable way regarding tendon regeneration; therefore, these medications should be used with more caution clinically.

Hyperferritinemia is associated with low incidence of graft versus host disease, high relapse rate, and impaired survival in patients with blood disorders receiving allogeneic hematopoietic stem cell grafts.

High pre-transplantation serum ferritin levels have been reported to be associated with impaired survival post-transplantation in patients with acute myeloid leukemia or myelodysplastic syndrome. We performed a retrospective study of 309 patients who underwent allogeneic hematopoietic stem cell transplantation at two transplantation centers. The aim was to determine the effect of pretransplantation hyperferritinemia on survival, graft versus host disease, and relapse. In both univariate and multivariate analysis, elevated ferritin levels were significantly associated with shorter overall and relapse-free survival times and increased relapse rate, but lower risk of chronic graft versus host disease. Elevated ferritin levels were not associated with non-relapse mortality. We hypothesize that ferritin may exert an immunosuppressive effect, reducing graft versus host disease and graft versus leukemia effects, resulting in increased risk of relapse and impaired survival.