Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Neonatal Lung Disease: Tiny Particles, Major Promise, Rigorous Requirements for Clinical Translation.

Extreme preterm birth disrupts late lung development and puts newborns at risk of developing chronic lung disease, known as bronchopulmonary dysplasia (BPD). BPD can be associated with life-long complications, and currently no effective treatment is available. Cell therapies are entering the clinics to curb complications of extreme preterm birth with several clinical trials testing the feasibility, safety and efficacy of mesenchymal stromal cells (MSCs). The therapeutic effect of MSCs is contained in their secretome, and nanosized membranous structures released by the MSCs, known as extracellular vesicles (EVs), have been shown to be the therapeutic vectors. Driven by this discovery, the efficacy of EV-based therapy is currently being explored in models of BPD. EVs derived from MSCs, contain a rich cargo of anti-inflammatory and pro-angiogenic molecules, making them suitable candidates to treat multifactorial diseases such as BPD. Here, we review the state-of-the-art of preclinical studies involving MSC-derived EVs in models of BPD and highlight technical and regulatory challenges that need to be addressed before clinical translation. In addition, we aim at increasing awareness regarding the importance of rigorous reporting of experimental details of EV experiments and to increase the outreach of the current established guidelines amongst researchers in the BPD field.