PROJECT: JTC 2025 - Pain: RESOLVE

The RESOLVE project develops mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) as targeted therapy for chronic neuropathic pain, which affects 20% of adults worldwide. Chronic pain is sustained by neuroinflammation and immune/glial dysregulation, while current treatments only offer symptomatic relief. MSC-EVs are potent immunomodulators that reprogram immune cells and glia, presenting a promising cell-free therapy. The work plan includes six packages: MSC-EVs from various sources will be screened in vitro, with top candidates tested in two animal models?chemotherapy-induced peripheral neuropathy in mice and experimental autoimmune neuritis in rats. Mechanistic studies will define how MSC-EVs modulate key inflammatory pathways (NF-?B, NLRP3, MAPKs, JAK-STAT) using transcriptomic and proteomic analyses. A clinical study will recruit 128 patients with immune-mediated neuropathies, collecting blood and cerebrospinal fluid to identify biomarkers of disease progression and therapeutic response. RESOLVE will define critical quality attributes and mechanisms of action for MSC-EV products, accelerating clinical translation and regulatory approval. Biomarker discovery will enable personalised medicine, improving patient stratification and monitoring. The project aims to deliver safer, more effective treatments for chronic pain, reduce healthcare costs, and improve quality of life.