Nanoparticle-based extracellular vesicles and stem cells: labelling, imaging and safety assessment

Nanoparticles (NPs) are transforming biomedical research thanks to their unique physicochemical properties, which enable precise interactions with biological systems and new tracking applications in regenerative therapy. This thesis investigates the use of NPs, specifically iron oxide and gold NPs, in combination with stem cells and extracellular vesicles (EVs) to optimize the non-invasive tracking of those therapeutic agents in preclinical models. Experiments in vitro and in vivo were conducted with iron oxide and gold NPs to evaluate their effectiveness in magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT). These findings suggest that combining NPs with EVs or stem cells can be useful for different imaging techniques and can provide a comprehensive view of the biodistribution and behaviour of therapeutic agents, expanding the possibilities for monitoring regenerative therapies. However, before any nanoparticle-labeled stem cell or EV-based therapy can be translated to the first-time-in-human (FTIH), rigorous preclinical safety assessments are mandatory. The OECD has been actively developing and adapting test guidelines for evaluating the safety of nanomaterials, including nanoparticle-labeled stem cells and extracellular vesicles. This thesis provides insight on the OECD Test Guidelines used to evaluate, as the first steps, the genotoxicity of possible therapeutic agent.