Mesenchymal Stem Cell (MSC)-based therapies for neonatal lung and brain injury – one size fits all?

Abstract MSC-based therapies have emerged as a highly promising approach for two of the most devastating consequences of perinatal insults such as extreme prematurity and perinatal asphyxia: bronchopulmonary dysplasia (BPD) and neonatal brain injury. Both conditions share a common pathophysiological basis of inflammation, oxidative stress, and disrupted progenitor cell function in critical windows of organ development. Exogenous MSC act primarily through their secretome, releasing extracellular vesicles, growth factors, and immunomodulatory mediators that attenuate injury and support organ development. Despite compelling preclinical evidence and early clinical feasibility and safety data, neither indication has yet achieved definitive proof of therapeutic efficacy in adequately powered randomised trials. This review summarises the current state of knowledge for MSC-based therapies for neonatal chronic lung disease and subsequently for brain injury, highlighting shared mechanisms, organ-specific considerations, and the path towards clinical implementation.