Therapeutic Potential of Mesenchymal Stem Cells and MSC-derived Extracellular Vesicles for Bronchopulmonary Dysplasia: From Preclinical Promise to Clinical Trials

Faezeh Sadat  Azad; Elham  Zare; Hanieh  Shafienia

doi:10.18502/wjpn.v7i2.20450

Faezeh Sadat Azad Department of Molecular Medicine, School of Advanced Medical Technologies, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Elham Zare Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Hanieh Shafienia Department of Molecular Medicine, School of Advanced Medical Technologies, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

DOI: https://doi.org/10.18502/wjpn.v7i2.20450

Keywords: Bronchopulmonary dysplasia, Mesenchymal stem cells, Extracellular vesicles

Abstract

Background: Bronchopulmonary dysplasia (BPD) is the most common respiratory complication in infants born extremely preterm. Despite advances in neonatal care, including improved respiratory support, nutrition, and infection control, no definitive cure for BPD has been identified. This study aimed to synthesize contemporary evidence on mesenchymal stem cell (MSC)-based strategies and MSC-derived extracellular vesicles (MSC-EVs) for BPD, and to discuss their* therapeutic therapeutic potential and remaining challenges.

Methods: This study reviews clinical and preclinical data across multiple models to evaluate the therapeutic effects of MSCs and MSC-EVs for the treatment of BPD.

Results: The reviewed literature highlights that both MSCs and MSC-EVs improve alveolar and vascular development, reduce inflammation and fibrosis, and mitigate pulmonary hypertension. MSC-EVs offer cell-free advantages, including reduced immunogenicity, lower tumorigenic risk, enhanced stability, and tunable targeting. Although MSCs and MSC-EVs hold substantial promise, Phase 1 safety data for EV-based therapies in neonates are lacking, underscoring the necessity of early clinical trials to define tolerability and pharmacodynamics.

Conclusion: Transformative advances have been made in the treatment of well-recognized BPD. The field is moving toward standardized EV production, definitive trial design, and exploration of MSC-EV–based therapies as safer, scalable medical countermeasures, with biomarker-guided patient selection and multi-omics integration to refine precision therapy for BPD.