Research projects

It is well established that mesenchymal stromal cells (MSC) through their paracrine activity, which is mediated, in part, by extracellular vesicles (EVs) has a remarkable therapeutic effectiveness in tissue regeneration and modulating the immune response. We aim at developing a cell-free therapy based on the production of synthetic nanocapsules (NCs) encapsulating active components identified from MSC-derived EVs cargo that will down-regulate inflammation, will assist the restoration of systemic immune homeostasis and improve the lung injury in a sepsis model. During the third year of the project we have studied the therapeutic effect of MSCs-derived EVs (from MSCs in normal and septic conditions) in an Acute Lung Injury (ALI) pre-clinical model. This, revealed a higher immunomodulatory effect from EVs secreted by lipopolysaccharide (LPS) primed MSCs, since the animals that received this type of EVs showed a reduced alveolar permeability, resulting in a reduced neutrophil infiltration in the intraalveolar space. Concerning the already produced and characterized nanocarrier that will be used for the delivery of pre-selected EVs’ components, we have studied the kinetics of content release, that showed release of HSA from the first day of incubation. In addition, we have demonstrated that our nanocarrier is suitable for aerosolization, as their mean size and morphology remains stable after nebulization.  We believe that those first steps are very promising towards a cell-free therapeutic strategy for sepsis, based on the specific proteins and miRNAs responsible for EVs main therapeutic effect and the development and characterization of a nanocarrier, that in the future, will make it an innovative and cell-free treatment for sepsis and lung injury related diseases.