Dr. rer. nat. Katharina Schmidt-Bleek

Immune modulatory approaches represent a novel therapeutic treatment stratagy in the context of fracture healing. Especially interferences in the early fracture healing phase could be done directly intra-operatively when a fracture is treated in the clinic, avoiding a stressful second surgery. For such an approach, a deeper characterisation of the patient and thus the identification of a potential impaired healer is indespensable  

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Investigation of detrimental immune cells

Examination of the number of CD8+ TEMRA cells over time revealed that the difference in CD8+ TEMRA cell number in patients with delayed healing reflects the individual's immune profile, rather than an acute fracture-related event. These cells specifically occur in the early fracture hematoma. Strikingly the depletion of CD8 + T cells improves bone regeneration, whereas adding CD8+ T cells impaires fracture healing. Hence, we focus on these CD8 + TEMRA cells as research target to serve as future marker for interventions in patients with delayed bone fracture healing.

[Englische Übersetzung] Erfassung der altersbedingten CD8+ TEMRA Zellzahl wies darauf hin, dass der Unterschied in der CD8+ TEMRA Zellzahl in Patienten mit verzögerter Heilung eher das individuelle Immunprofil wiederspiegelte, anstatt ein akutes frakturbezogenes Ereignis. Diese Zellen treten spezifisch in dem frühen Frakturhämatom auf. Bemerkenswerterweise verbesserte die Depletion der CD8+ T-Zellen die Knochenregeneration, wohingegen die Zugabe von CD8+ T-Zellen die Frakturheilung beeinträchtigte. Deshalb fokussieren wir uns auf die CD8+ TEMRA Zellen als wissenschaftlichen Ansatzpunkt, um als zukünftiger Marker zu dienen für die Behandlung von Patienten mit verzögerter Knochenfrakturheilung.

Cell therapy with supportive immune cells

Regulatory T-cells (Tregs) are an anti-inflammatory cell type as they secrete factors, which suppress pro-inflammatory cells like the CD8+ T-cells. In our group we investigate the possibility to improve the fracture healing outcome by the application of Tregs. A deeper understanding of the mode of action of Tregs in the course of fracture healing could be used in the future in clinical applications to help patients with an impaired healing situation.

Pharmacological immune modulation

Application of Immunmodulatory Factors to support fracture healing is also a focus of our group. Such factors are among others protein-based Interleukins or Antibodies, which target specific cell types and can suppress them. They can also induce a polarization of Immune cells towards a beneficial anti-inflammatory type, like in Macrophages. Whereas antibodies can even deplete entire cell fractions, like the unwanted CD8+ T-Cells. Furthermore, we focus on small signalling molecules, which are already applied in the clinics, and which further revealed anti-inflammatory properties recently. They can suppress pro-inflammatory cells and/or stimulate anti-inflammatory cellular responses. For the application of immunemodulatory factors we investigate local releases from biomaterials besides intravenious injections.