Postdoctoral fellow North Carolina State University Raleigh, North Carolina
Characterizing the Cytokine Environment in Acute Tendon Injury to Enhance Mesenchymal Stem Cell Therapy. Koch DW1, Messenger KM2, Berglund AK1, Gilbertie JM1, Ellis IM1, Schnabel LV1. 1North Carolina State University, Department of Clinical Sciences, Raleigh, NC; 2North Carolina State University, Department of Molecular Biomedical Sciences, Raleigh, NC.
Tendon injury in the horse commonly affects the superficial digital flexor tendon (SDFT). Although mesenchymal stem cell (MSC) therapy has improved clinical and experimental SDFT lesions, the mechanism of this effect is still largely unknown. Recent evidence suggests that MSCs secrete regenerative molecules following inflammatory stimulation. However, because the cytokine profile in acute tendon injury has been poorly characterized, optimal timing of MSC therapy is unknown. In an equine model of acute tendon injury, our objective was to track the temporal change in inflammatory cytokines with the hypothesis that these inflammatory cytokines change over time. Horses underwent surgical induction of bilateral forelimb SDFT lesions and implantation of an ultrafiltrate probe (n = 6) with a single control (n = 1). Tendon ultrafiltrate was collected from the ultrafiltrate probes immediately postoperative and every 12 hours thereafter for 21 days. Pro-inflammatory cytokines interleukin-1 beta (IL-1β), -6, and -8 along with fibroblast growth factor-2 (FGF-2) were noted to peak by 48 hours. Our data support our hypothesis that a temporal change in inflammatory cytokines occur following acute tendon injury. Continued in vitro work from our lab will examine the MSC secretome following stimulation with a cytokine profile that mimics the peak- or post-inflammatory period quantified here to determine if MSC therapy in tendon injury can be enhanced. Limitations include inconsistent tendon ultrafiltrate collection and inability to collect percutaneous samples from the control. We have shown that inflammation peaks within the first 48 hours following tendon injury which could provide a more optimal microenvironment for administration of MSCs.