Therapeutic potential of products derived from mesenchymal stem/stromal cells in pulmonary disease

Multipotent mesenchymal stem/stromal cells (MSCs) possess robust self-renewal characteristics and the ability to differentiate into tissue-specific cells. Their therapeutic potential appears promising as evident from their efficacy in several animal models of pulmonary disorders as well as early-phase clinical trials of acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). Such therapeutic efficacy might be attributed to MSC-derived products (the "secretome"), namely conditioned media (CM) and extracellular vesicles (EVs), which have been shown to play pivotal roles in the regenerative function of MSCs. Importantly, the EVs secreted by MSCs can transfer a variety of bioactive factors to modulate the function of recipient cells via various mechanisms, including ligand-receptor interactions, direct membrane fusion, endocytosis, or phagocytosis.Herein, we review the current state-of-the-science of MSC-derived CM and EVs as potential therapeutic agents in lung diseases. We suggest that the MSC-derived secretome might be an appropriate therapeutic agent for treating aggressive pulmonary disorders because of biological and logistical advantages over live cell therapy. Nonetheless, further studies are warranted to elucidate the safety and efficacy of these components in combating pulmonary diseases.