Lung mesenchymal stromal cells in development and disease: to serve and protect?

SIGNIFICANCE: Bronchopulmonary dysplasia (BPD) is a disease of the developing lung that afflicts extreme preterm infants in the neonatal intensive care unit. Follow-up studies into adulthood show that BPD is not merely a problem of the neonatal period, as it also may predispose to early-onset emphysema and poor lung function in later life. RECENT ADVANCES: The increasing promise of bone marrow- or umbilical cord-derived mesenchymal stromal cells (MSCs) to repair neonatal and adult lung diseases may for the first time offer the chance to make substantial strides in improving the outcome of extreme premature infants at risk of developing BPD. As more knowledge has been obtained on MSCs over the past decades, it has become clear that each organ has its own reservoir of endogenous MSCs, including the lung. CRITICAL ISSUES: We have only barely scratched the surface on what resident lung MSCs exactly are and what their role and function in lung development may be. Moreover, what happens to these putative repair cells in BPD when alveolar development goes awry and why do their counterparts from the bone marrow and umbilical cord succeed in restoring normal alveolar development when they themselves do not? FUTURE DIRECTIONS: Much work remains to be carried out to validate lung MSCs, but with the high potential of MSC-based treatment for BPD and other lung diseases, a thorough understanding of the endogenous lung MSC will be pivotal to get to the bottom of these diseases.