Lung derived extracellular vesicles have distinct pro-repair effects, depending on the age of their source tissue
Many age-related lung diseases encompass aberrant repair mechanisms. To develop novel treatments for these diseases, it is critical to understand how biology and repair signals are altered in aged lungs. Extracellular vesicles (EVs) carry bioactive signals reflecting their source tissue; therefore, we used EVs derived from precision-cut lung slices (PCLS) as tools to investigate differences in lung biology and repair signals that occur upon ageing and injury. We compared the physicochemical properties and biological content of four groups of EVs, obtained from uninjured and injured, young and aged PCLS. Treatment with EVs obtained from young, uninjured (YU) PCLS decreased apoptotic cells in both young and aged spatially injured (AIR)-PCLS. YU EVs also increased the percentage of alveolar progenitor cells in aged AIR-PCLS, indicating that aged lungs retain the capacity to mount a repair response, if provided with the right biological cues. Small RNA sequencing revealed the miRNA content of each EV group is altered, depending on the physiological conditions of their source tissue. Bioinformatic analysis of the target genes regulated by differentially expressed miRNAs identified enrichment of genes required for lung development and repair. These findings pave the way for future therapeutic strategies to repair or regenerate aged lungs. Overall design: Small RNA-sequencing of total RNA content of extracellular vesicles (EVs) derived from uninjured and acid-injured, aged and young adult mouse precision-cut lung slices (PCLS).