A 3D Dynamic In Vitro Model of Inflammatory Tendon Disease.

Three-dimensional (3D) cell cultures combining multipotent mesenchymal stromal cells (MSC), tendon extracellular matrix scaffolds, and mechanical stimulation by a bioreactor have been used to induce tenogenic differentiation in vitro. Yet, these conditions alone do not mimic the environment of acute inflammatory tendon disease adequately, thus the results of such studies are not representatives for tendon regeneration after acute injury. In this chapter, we describe two different approaches to introduce inflammatory stimuli, comprising co-culture with leukocytes and supplementation with the cytokines IL-1 ß and TNF-α. The presented in vitro model of inflammatory tendon disease could be used to study musculoskeletal pathophysiology and regeneration in more depth.

Tenogenic Properties of Mesenchymal Progenitor Cells Are Compromised in an Inflammatory Environment.

Transplantation of multipotent mesenchymal progenitor cells is a valuable option for treating tendon disease. Tenogenic differentiation leading to cell replacement and subsequent matrix modulation may contribute to the regenerative effects of these cells, but it is unclear whether this occurs in the inflammatory environment of acute tendon disease. Equine adipose-derived stromal cells (ASC) were cultured as monolayers or on decellularized tendon scaffolds in static or dynamic conditions, the latter represented by cyclic stretching. The impact of different inflammatory conditions, as represented by supplementation with interleukin-1ß and/or tumor necrosis factor-α or by co-culture with allogeneic peripheral blood leukocytes, on ASC functional properties was investigated. High cytokine concentrations increased ASC proliferation and osteogenic differentiation, but decreased chondrogenic differentiation and ASC viability in scaffold culture, as well as tendon scaffold repopulation, and strongly influenced musculoskeletal gene expression. Effects regarding the latter differed between the monolayer and scaffold cultures. Leukocytes rather decreased ASC proliferation, but had similar effects on viability and musculoskeletal gene expression. This included decreased expression of the tenogenic transcription factor scleraxis by an inflammatory environment throughout culture conditions. The data demonstrate that ASC tenogenic properties are compromised in an inflammatory environment, with relevance to their possible mechanisms of action in acute tendon disease.