Available online 12 March 2023, 151724

Author links open overlay panelAbstract

Lung diseases are a main cause of mortality and morbidity in neonates. Despite major breakthroughs, therapies remain supportive and, in some instances, contribute to lung injury. Because the neonatal lung is still developing, the ideal therapy should be capable of preventing/repairing lung injury while at the same time, promoting lung growth. Cell-based therapies hold high hopes based on laboratory experiments in animal models of neonatal lung injury. Mesenchymal stromal cells and amnion epithelial cells are now in early phase clinical trials to test the feasibility, safety and early signs of efficacy in preterm infants at risk of developing bronchopulmonary dysplasia. Other cell-based therapies are being explored in experimental models of congenital diaphragmatic hernia and alveolar capillary dysplasia. This review will summarize current evidence that has lead to the clinical translation of cell-based therapies and highlights controversies and the numerous questions that remain to be addressed to harness the putative repair potential of cell-based therapies.

Section snippetsNEONATAL LUNG DISEASES IN NEED OF SPECIFIC THERAPIES

Preterm birth is a leading cause of infant morbidity and mortality worldwide1. Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity that follows ventilator and oxygen therapy for acute respiratory failure, is the most common complication of extreme prematurity and lacks effective treatment2. Advances in perinatal care enable the survival of premature infants born at increasingly earlier stages of gestation. BPD is a complex, multi-factorial disease in which inflammation,

CELL THERAPIES FOR NEONATAL LUNG DISEASES

Stem cells are defined by their capacity to self-renew and to differentiate into various cell types. For example, hematopoietic stem cells, the first stem cells identified in 1961 by Till and McCulloch, self-renew over a life time and produce erythrocytes, white blood cells and platelets12. It is this capacity of self-renewal and differentiation potential that regenerative medicine seeks to harness in its cell therapy branch. Over the past 15 years, numerous cell therapies have been explored in

REMAINING QUESTIONS AND UNCERTAINTIES

The time seems to be ripe to initiate well-designed early phase clinical trials based on strong rationale and biological plausibility. However, the discrepancy between very promising preclinical studies and the rather dismal results of clinical trials with MSCs in the adult literature72,73, highlight the importance of clarifying a number of critical questions pertaining to the biology of putative repair cells.

Declaration of Competing Interest

The authors report no conflicts of interest

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