Using immune cells to improve the inflamatory reaction during bone healing
Bone fracture healing is a role model for successful endogenous regeneration, but delayed healing or non-union is a relevant clinical problem even when optimal medical treatment is available. The Federal Office of Statistics recorded 802,662 fractures in Germany in the year 2014, with 38% of the patients with fractures of the extremities older than 75 years. This indicates that bone injury is increasingly a problem occurring in elderly. Elderly patients always have an experienced (“aged”) immune system with enhanced frequencies of memory/effector cells of the adaptive immunity, thus they are in a constant systemic pro-inflammatory state. This elevated pro-inflammatory state could be a cause for the high percentages of disturbed bone healing in elderly. Fracture healing is a multistage healing process involving complex and well-orchestrated steps. In a joint effort K. Schmidt-Bleek and H-D. Volk were able to show that immune cells partake in bone healing, that they can have detrimental or beneficial effects on healing and that they also influence the resulting bone quality.
A balanced immune response is important for successful healing. Cells with a high anti-inflammatory capacity could represent a source useful to enhance bone healing.
Hypothesis of this PhD work is that anti-inflammatory immune cells can be increased locally to enhance bone healing. Research will include the impact of an experienced immunity that causes a pro-inflammatory milieu resembling the immune composition of aged patients. The impact of the immune experience will be analysed and a possible therapeutic approach using immune cells to optimize the inflammatory reaction within the healing process will be the topic of this PhD thesis.
1. Schlundt C, Reinke S, Geissler S, Bucher CH, Giannini C, Märdian S, Dahne M, Kleber C, Samans B, Baron U, Duda GN, Volk HD, Schmidt-Bleek K. Individual Effector/Regulator T Cell Ratios Impact Bone Regeneration. Front Immunol. 2019.10:1954.
2. Bucher CH, Schlundt C, Wulsten D, Sass FA, Wendler S, Ellinghaus A, Thiele T, Seemann R, Willie BM, Volk HD, Duda GN, Schmidt-Bleek K. Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodel-ing, and Healing. Front Immunol. 2019. 10:797.