Magnetic engineered bone mesenchymal stem cells-derived exosomes for targeted acute lung injury therapy

Acute lung injury (ALI) is a critical pulmonary condition characterized by high morbidity and mortality rates. Recent studies have highlighted the therapeutic potential of engineered exosomes derived from mesenchymal stem cell (MSC) in modulating the inflammatory response in ALI. Here, a novel approach was developed to fabricate engineered bone mesenchymal stem cells (BMSCs) derived exosomes by utilizing superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF) to precondition BMSCs. This study evaluated and compared the therapeutic potential of different groups of engineered exosomes in ALI mice model and analyzed their underlying mechanisms using high-throughput sequencing. BMSCs were isolated from SD rats and subjected to treatment with SPIONs and/or an AMF. Following this, we established a lipopolysaccharide (LPS)-induced ALI mice model and evaluated the therapeutic efficacy of exosomes from different groups by administering them via tail vein injection. The expression profiles of microRNAs (miRNAs) in exosomes were compared to explore the mechanism of regulating inflammatory response and ameliorating lung injury. 25 µg/mL SPIONs and 3mT AMF were the best conditions for preparing engineered exosomes, which reduced the level of pro-inflammatory factors and had the most significant effect in repaired lung damage in vivo. The transfection of miR-145-5p mimics enhanced Bronchial Epithelium transformed with Ad12-SV40 2B (BEAS-2B) cells viability and reduced relevant inflammation expression in vitro experiments. The engineered exosomes obtained by low dose SPIONs combined with AMF can help regulate the level of inflammatory factors and improve lung injury. Targeted regulation of kruppel-like factor 5 (KLF5) by exosomal miR-145-5p and inhibition of the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway play a key role in this vitro process.