Therapeutic targeting of small extracellular vesicle (sEV) release and uptake in post-traumatic hyper-inflammation (A06)

• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery ; Cell Biology
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 251293561

Major physical trauma can trigger a local, but also an unbalanced systemic immune response with organ dysfunction. Here, we demonstrate that increased release of small extracellular nanovesicles (sEVs, exosomes) from endothelial cells with pro-inflammatory mRNAs after severe TXT propagates systemic inflammation, and this is normalized by inhibition of sEV-biogenesis. We hypothesize that blocking sEV-release and -uptake in target cells with clinically approved inhibitors, or abrogated loading of pro-inflammatory cargo will ameliorate inflammation. Therefore, we will perform a drug repurposing screen and engineer targeted therapeutic sEVs with siRNAs to block pro-inflammatory sEV-based reprogramming.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1149: Danger Response, Disturbance Factors and Regenerative Potential after Acute Trauma
• Applicant Institution: Universität Ulm
• Project Head: Professor Dr. Thomas Seufferlein