Lung derived extracellular vesicles have distinct pro-repair effects, depending on the age of their source tissue

Abstract

Abstract 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 precision-cut lung slices (PCLS)-derived EVs 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 EVs obtained from uninjured and injured, young and aged mouse PCLS. Treatment with EVs from young, uninjured (YU) PCLS decreased apoptotic cells in both young and aged spatially acid-injured (AIR)-PCLS. YU EVs 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 provide mechanistic insight into the content of young versus aged lung EVs, that could be leveraged for regenerative medicine strategies.