Sperimentazione clinica di fase I, in aperto e a braccio singolo, con progressivo incremento della dose, finalizzata a valutare la sicurezza e la tollerabilità della somministrazione di vescicole extracellulari derivate da cellule mesenchimali allogeniche di cordone ombelicale per la prevenzione della displasia broncopolmonare nei neonati estremamente pretermine: dati preliminari

Preterm birth is a complex process influenced by environmental and genetic factors, associated with both acute and chronic complications, among which bronchopulmonary dysplasia (BPD) represents the most frequent and severe. BPD is a multifactorial respiratory disorder characterized by disruption of alveolarization and microvascular development, resulting in impaired gas exchange and lung mechanics. Current preventive and therapeutic strategies, although having improved survival of extremely preterm infants, have not significantly reduced the incidence of the disease. Preclinical evidence has demonstrated that extracellular vesicles (EVs) exert anti-inflammatory and immunomodulatory effects, influence the pathogenesis of BPD, and favorably impact developmental processes at the pulmonary level and beyond, with pleiotropic effects, including on the brain. Based on these premises, an international multicenter phase I–II clinical trial has been designed to investigate the use of EXOB-001, a preparation of EVs derived from umbilical cord tissue–derived mesenchymal stem cells, with the primary aim of evaluating its safety and efficacy in extremely preterm infants at high risk of developing BPD. This doctoral project focused on the phase I study, which involves the enrollment of dose-escalating cohorts receiving single or triple administrations, with assessment of dose-limiting toxicities and comparison of clinical outcomes with a nested historical cohort. Monitoring activities included acute and medium-term safety parameters, incidence and severity of BPD, echocardiographic and pulmonary assessments, as well as respiratory and neurodevelopmental outcomes up to two years of corrected age. Interim analysis of the available data confirmed a favorable tolerability profile of EXOB-001, with no dose-limiting toxicities and no serious adverse events attributable to the treatment. Patient recruitment in phase I is still ongoing. These preliminary results support the feasibility of the study and highlight the potential role of EVs as a novel preventive strategy for BPD, paving the way for further efficacy evaluations in subsequent study phases.