Nebulised MSC-Derived EVs: A Potential Therapy for E. coli-Induced Pneumonia

     Mesenchymal stem cells (MSCs) have shown great promise in cell therapy for various diseases, including lung injury. However, recent research has focused on the therapeutic potential of extracellular vesicles (EVs) derived from MSCs. These EVs contain bioactive molecules that can modulate immune responses and promote tissue repair. In the context of pneumonia caused by Escherichia coli (E. coli) infection, a recent study by Gonzalez et al (2023) aimed to investigate whether nebulised MSC-EVs could be an effective treatment. They hypothesised that nebulised MSC-EVs would retain their therapeutic properties and offer a novel delivery route to alleviate lung injury associated with E. coli pneumonia.

To assess the effects of nebulisation on MSC-EVs, the researchers examined the size, surface markers, and miRNA content of the EVs before and after nebulisation. In vitro experiments involved exposing lung cells to lipopolysaccharide (LPS), a component of E. coli, and treating them with nebulised MSC-EVs derived from bone marrow (BM) or umbilical cord (UC) sources. Cell viability and inflammatory cytokine levels were measured to evaluate the therapeutic effects of the EVs.

Further investigations were conducted using THP-1 monocytes stimulated with LPS and treated with nebulised BM- or UC-EVs to assess phagocytosis activity. In vivo experiments were performed using bth mouse and rat models. Mice were intratracheally administered LPS and subsequently received intravenous (IV) administration of BM- or UC-EVs. Injury markers were assessed after 24 hours. Rats were intratracheally instilled with E. coli bacteria and received IV or direct nebulisation of BM- or UC-EVs using the flexiVent system. Lung damage was evaluated through physiological parameters, histology, and inflammatory marker presence after 48 hours.

This study found that nebulised MSC-EVs retained their immunomodulatory and wound healing capacity in vitro. The integrity and content of the EVs were preserved after nebulisation. Treatment with IV or nebulised MSC-EVs reduced the severity of LPS-induced lung injury and E. coli-induced pneumonia. These effects were demonstrated by a reduction in bacterial load and edema, improved blood oxygenation, and enhanced lung histological scores. Animals treated with MSC-EVs also showed lower levels of inflammatory cytokines and inflammatory-related markers.