Looking at the developing lung in single-cell resolution.

Lung development is a complicated and delicate process, facilitated by spatially and temporarily coordinated cross talk of up to 40 cell types. Developmental origin and heterogeneity of lung cell lineages in context of lung development have been a focus of research efforts for decades. Bulk RNA and protein measurements, RNA and protein labeling, and lineage tracing techniques have been traditionally employed. However, the complex and heterogeneous nature of lung tissue presents a particular challenge when identifying subtle changes in gene expression in individual cell types. Rapidly developing single-cell RNA sequencing (scRNA-seq) techniques allow for unbiased and robust assessment of complex cellular dynamics during biological processes in unprecedented ways. Discovered a decade ago, scRNA-seq has been applied in respiratory research to understand lung cellular composition and to identify novel cell types. Still, very few studies to date have addressed the single-cell transcriptome in healthy or aberrantly developing lung. In this review, we discuss principal discoveries with scRNA-seq in the field of prenatal and postnatal lung development. In addition, we examine challenges and expectations, and propose future steps associated with the use of scRNA-seq to study developmental lung diseases.

Altered breathing mechanics and ventilatory response during exercise in children born extremely preterm.

BACKGROUND: Extreme preterm birth confers risk of long-term impairments in lung function and exercise capacity. There are limited data on the factors contributing to exercise limitation following extreme preterm birth. This study examined respiratory mechanics and ventilatory response during exercise in a large cohort of children born extremely preterm (EP). METHODS: This cohort study included children 8-12 years of age who were born EP (≤28 weeks gestation) between 1997 and 2004 and treated in a large regionalised neonatal intensive care unit in western Canada. EP children were divided into no/mild bronchopulmonary dysplasia (BPD) (ie, supplementary oxygen or ventilation ceased before 36 weeks gestational age; n=53) and moderate/severe BPD (ie, continued supplementary oxygen or ventilation at 36 weeks gestational age; n=50). Age-matched control children (n=65) were born at full term. All children attempted lung function and cardiopulmonary exercise testing measurements. RESULTS: Compared with control children, EP children had lower airway flows and diffusion capacity but preserved total lung capacity. Children with moderate/severe BPD had evidence of gas trapping relative to other groups. The mean difference in exercise capacity (as measured by oxygen uptake (VO2)% predicted) in children with moderate/severe BPD was -18±5% and -14±5.0% below children with no/mild BPD and control children, respectively. Children with moderate/severe BPD demonstrated a potentiated ventilatory response and greater prevalence of expiratory flow limitation during exercise compared with other groups. Resting lung function did not correlate with exercise capacity. CONCLUSIONS: Expiratory flow limitation and an exaggerated ventilatory response contribute to respiratory limitation to exercise in children born EP with moderate/severe BPD.

Functional inhibition of PAR2 alleviates allergen-induced airway hyperresponsiveness and inflammation.

BACKGROUND: Proteinase-activated receptor 2 (PAR2 ) is a G protein-coupled receptor activated by trypsin-like serine proteinases. PAR2 activation has been associated with inflammation including allergic airway inflammation. We have also shown that PAR2 activation in the airways leads to allergic sensitization. The exact contribution of PAR2 in the development of eosinophilic inflammation and airway hyperresponsiveness (AHR) in sensitized individuals is not clear. OBJECTIVE: To investigate whether functional inhibition of PAR2 during allergen challenge of allergic mice would inhibit allergen-induced AHR and inflammation in mouse models of asthma. METHODS: Mice were sensitized and challenged with ovalbumin (OVA) or cockroach extract (CE). To investigate the role of PAR2 in the development of AHR and airway inflammation, we administered blocking anti-PAR2 antibodies, or a cell permeable peptide inhibitor of PAR2 signalling, pepducin, i.n. before allergen challenges and then assessed AHR and airway inflammation. RESULTS: Administration of anti-PAR2 antibodies significantly inhibited OVA- and CE-induced AHR and airway inflammation. In particular, two anti-PAR2 antibodies, the monoclonal SAM-11 and polyclonal B5, inhibited AHR, airway eosinophilia, the increase of cytokines in the lung tissue and antigen-specific T cell proliferation, but had no effect on antigen-specific IgG and IgE levels. Pepducin was also effective in inhibiting AHR and airway inflammation in an OVA model of allergic airway inflammation. CONCLUSIONS AND CLINICAL RELEVANCE: Functional blockade of PAR2 in the airways during allergen challenge improves allergen-induced AHR and inflammation in mice. Therefore, topical PAR2 blockade in the airways, through anti-PAR2 antibodies or molecules that interrupt PAR2 signalling, has the potential to be used as a therapeutic option in allergic asthma.

Perinatal origins of bronchopulmonary dysplasia-deciphering normal and impaired lung development cell by cell.

Bronchopulmonary dysplasia (BPD) is a multifactorial disease occurring as a consequence of premature birth, as well as antenatal and postnatal injury to the developing lung. BPD morbidity and severity depend on a complex interplay between prenatal and postnatal inflammation, mechanical ventilation, and oxygen therapy as well as associated prematurity-related complications. These initial hits result in ill-explored aberrant immune and reparative response, activation of pro-fibrotic and anti-angiogenic factors, which further perpetuate the injury. Histologically, the disease presents primarily by impaired lung development and an arrest in lung microvascular maturation. Consequently, BPD leads to respiratory complications beyond the neonatal period and may result in premature aging of the lung. While the numerous prenatal and postnatal stimuli contributing to BPD pathogenesis are relatively well known, the specific cell populations driving the injury, as well as underlying mechanisms are still not well understood. Recently, an effort to gain a more detailed insight into the cellular composition of the developing lung and its progenitor populations has unfold. Here, we provide an overview of the current knowledge regarding perinatal origin of BPD and discuss underlying mechanisms, as well as novel approaches to study the perturbed lung development.

Methylprednisolone, an alternative to dexamethasone in very premature infants at risk of chronic lung disease.

OBJECTIVE: To evaluate the benefits and the medium-term side effects of methylprednisolone in very preterm infants at risk of chronic lung disease. STUDY DESIGN: Forty-five consecutive preterm infants (< 30 weeks' gestation) at risk of chronic lung disease were treated at a mean postnatal age of 16 days with a tapering course of methylprednisolone. The outcome of treatment was assessed by comparison with 45 consecutive historical cases of infants treated with dexamethasone; the infants did not differ in baseline characteristics. RESULTS: There were no differences between groups in the rate of survivors without chronic lung disease. Infants treated with methylprednisolone had a higher rate of body weight gain during the treatment period (median 120 g, range 0 to 190, vs. 70 g, range -110 to 210, P = 0.01) and between birth and the age of 40 weeks (median 1660 g, range 1170-2520, vs. 1580 g, range 1,040 to 2,120, P = 0.02). The incidence of both glucose intolerance requiring insulin (0 % vs. 18 %, P = 0.006) and cystic periventricular leukomalacia (2 % vs. 18%, P = 0.03) was lower among methylprednisolone-treated infants. CONCLUSION: Our observations confirm methylprednisolone to be as effective as dexamethasone and to have fewer side effects. A randomized control trial is needed to further study the efficacy and safety of methylprednisolone in very premature infants at risk of chronic lung disease.

Congenital diaphragmatic hernia: antenatal prognostic factors. Does cardiac ventricular disproportion in utero predict outcome and pulmonary hypoplasia?

UNLABELLED: Despite regular progress in neonatal intensive care, congenital diaphragmatic hernia (CDH) diagnosed antenatally is still associated with up to 80% mortality. It is impossible to predict which fetus with CDH will survive or not. OBJECTIVE: To identify reliable antenatal predictors of outcome and of pulmonary hypoplasia (PH) in fetuses with CDH. DESIGN: Retrospective study. SETTING: Paediatric intensive care unit of a university children's hospital. PATIENTS AND METHODS: Antenatal parameters and presence of left ventricular hypoplasia in utero were compared retrospectively to outcome and to presence of PH in 32 consecutive newborn infants with antenatally diagnosed CDH. Antenatal parameters included: gestational age at diagnosis, herniated organs, associated malformations and presence of polyhydramnios. Size of the cardiac ventricles, the aorta (Ao) and the pulmonary artery (PA) were obtained by fetal echocardiography, from which we calculated a cardioventricular index (left ventricle/right ventricle, LV/RV) and a cardiovascular index (Ao/PA). Delivery was planned in order to provide ventilatory and hemodynamic management. In case of death, PH was assessed according to the following criteria: the lung weight/body weight index and the radial alveolar count. For statistical comparisons, patients were separated into two groups: the hypoplasia group (H) and the non-hypoplasia group (NH). RESULTS: Thirty-two pregnancies were delivered. Twenty-six newborns died (81%), 6 survived (19%). When comparing non-survivors to survivors, predictors of poor outcome were: mean gestational age at diagnosis (23 vs 28 weeks, p = 0.002), intrathoracic stomach (20 vs 1 s, p = 0.01) and associated malformations (6 vs 0). Cardiac ventricular disproportion, expressed by the LV/RV ratio, appeared to correlate well with a poor outcome (0.63 in non-survivors vs 0.93 in survivors, p = 0.03) and with PH (0.63 in the H group vs 0.95 in the NH group, p = 0.03). CONCLUSIONS: Our study confirmed the factors for a poor prognosis associated with CDH previously described in the literature, but none with a consistent demonstration of accuracy. LV hypoplasia may be a more accurate predictor of outcome and of PH but it has to be assessed by prospective studies with larger samples. Further basic science and Doppler-flow studies may be helpful to understand the natural history and pathophysiology of LV hypoplasia in CDH.

Congenital diaphragmatic hernia: antenatal prognostic factors : Does cardiac ventricular disproportion in utero predict outcome and pulmonary hypoplasia?

UNLABELLED: Despite regular progress in neonatal intensive care, congenital diaphragmatic hernia (CDH) diagnosed antenatally is still associated with up to 80 % mortality. It is impossible to predict which fetus with CDH will survive or not. OBJECTIVE: To identify reliable antenatal predictors of outcome and of pulmonary hypoplasia (PH) in fetuses with CDH. DESIGN: Retrospective study. SETTING: Paediatric intensive care unit of a university children's hospital. PATIENTS AND METHODS: Antenatal parameters and presence of left ventricular hypoplasia in utero were compared retrospectively to outcome and to presence of PH in 32 consecutive newborn infants with antenatally diagnosed CDH. Antenatal parameters included: gestational age at diagnosis, herniated organs, associated malformations and presence of polyhydramnios. Size of the cardiac ventricles, the aorta (Ao) and the pulmonary artery (PA) were obtained by fetal echocardiography, from which we calculated a cardioventricular index (left ventricle/right ventricle, LV/RV) and a cardiovascular index (Ao/PA). Delivery was planned in order to provide ventilatory and hemodynamic management. In case of death, PH was assessed according to the following criteria: the lung weight/body weight index and the radial alveolar count. For statistical comparisons, patients were separated into two groups: the hypoplasia group (H) and the non-hypoplasia group (NH). RESULTS: Thirty-two pregnancies were delivered. Twenty-six newborns died (81 %), 6 survived (19 %). When comparing non-survivors to survivors, predictors of poor outcome were: mean gestational age at diagnosis (23 vs 28 weeks, p = 0.002), intrathoracic stomach (20 vs 1 s, p = 0.01) and associated malformations (6 vs 0). Cardiac ventricular disproportion, expressed by the LV/RV ratio, appeared to correlate well with a poor outcome (0.63 in non-survivors vs 0.93 in survivors, p = 0.03) and with PH (0.63 in the H group vs 0.95 in the NH group, p = 0.03). CONCLUSIONS: Our study confirmed the factors for a poor prognosis associated with CDH previously described in the literature, but none with a consistent demonstration of accuracy. LV hypoplasia may be a more accurate predictor of outcome and of PH but it has to be assessed by prospective studies with larger samples. Further basic science and Doppler-flow studies may be helpful to understand the natural history and pathophysiology of LV hypoplasia in CDH.

Haemorrhagic shock and encephalopathy syndrome: neurological course and predictors of outcome.

UNLABELLED: The haemorrhagic shock and encephalopathy syndrome (HSES) is a devastating disease. The aetiology of this syndrome is unknown, and, despite intensive treatment, the outcome is often fatal or associated with severe neurological sequelae. OBJECTIVE: To assess the neurological features and potential prognostic markers of the disease. DESIGN: Retrospective study. SETTING: Division of Neuropaediatrics in a children's university hospital. PATIENTS AND METHODS: Fourteen patients fulfilling the HSES criteria out of 42 children admitted with fever and shock to the Paediatric Intensive Care Unit between 1986 and 1994, were analysed for clinical, biological, neuroradiological, EEG and neuropathological findings. RESULTS: The patients (age range from 2 to 33 months) were found at night or in the morning either comatous (n = 3) or convulsing (n = 11). All but one were healthy before admission, although eight had had a brief prodromal infectious disease. All were febrile (mean body temperature 39.9 degrees C +/-0.9 degrees). Seasonal clustering during the winter months was observed. Coma and seizures with frequent status epilepticus were the main neurological manifestations. All children recovered from their multiple organ failure within a few days. Seven died (50%); four survivors had neurological sequelae (29%) with a developmental quotient (DQ) of 50% or less in three and a DQ of 75% in one and three infants (21%) had normal outcomes. Computed tomography (CT) displayed a diffuse area of low density mainly in the cerebral cortex and intraventricular and parenchymal haemorrhages. Magnetic resonance imaging (MRI) showed haemorrhagic cortical lesions. Postmortem examination of the brain conducted in three patients showed necrotic and haemorrhagic lesions, mainly in cortical areas. Comparison of the children with adverse outcome (death or neurological sequelae) with those with normal outcome revealed that predictors of poor outcome were status epilepticus (p = 0.003) and coma for more than 24 h (p = 0.01). Infants without disseminated intravascular coagulation, without a biphasic course and without brain hypodensities or haemorrhages on CT scans performed at least 4 days after onset had a normal neurodevelopmental outcome. CONCLUSION: The central nervous system appeared to be the main target of the HSES lesions. The most common outcome was brain death or severe brain damage. Further studies with a larger sample are necessary to determine whether the prognostic indicators we identified are reliable.

Dypiridamole, a cGMP phosphodiesterase inhibitor, transiently improves the response to inhaled nitric oxide in two newborns with congenital diaphragmatic hernia.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) remains a frustrating cause of respiratory failure associated with persistent pulmonary hypertension of the newborn (PPHN). Although inhaled nitric oxide (iNO) is effective in many infants with PPHN, it often fails to improve oxygenation in infants with CDH. As the increase in vascular smooth muscle cyclic guanosine monophosphate (cGMP) in response to iNO may be impeded by increased phosphodiesterase type-V (PDE-V) activity, it has been suggested that PDE-V blockade potentiates the efficiency of iNO. CASE REPORTS: We used dypiridamole (Persantine), a specific PDE-V inhibitor, in two patients with CDH. Prenatal diagnosis showed a left-sided CDH at 23 weeks of gestation (GA) with intrathoracic stomach and left heart underdevelopment in the one infant and a right-sided CDH at 26 weeks GA with intrathoracic liver in the other. After antenatal corticoids, planned delivery was performed by the vaginal route at 38 weeks GA. Preoperative stabilization was achieved by high frequency oscillation, iNO and inotropic support over 24 h. Both had early pneumothorax drained by a chest tube. Despite optimization of ventilatory and hemodynamic support with surfactant replacement, iNO and adrenaline, oxygenation worsened progressively. Dypiridamole was introduced intravenously at 27 and 40 h, respectively, and improved oxygenation over the next 12 h. However, oxygenation again deteriorated and both patients died. CONCLUSION: Dypiridamole enhanced the response to iNO in PPHN associated with CDH, although this effect was transient. Combined therapy of iNO with PDE-V inhibitors may improve pulmonary vasodilation in some forms of PPHN which do not respond to iNO, thereby reducing the need for extracorporeal membrane oxygenation (ECMO) and improving outcome.

[Purulent pericarditis in children: a 15 year-experience]. / Les péricardites purulentes de l'enfant: 15 ans d'expérience.

BACKGROUND: Purulent pericarditis is rare in developed countries, but its prognosis is regarded as serious. Early diagnosis and appropriate treatment should prevent complications. PATIENTS: Among the 119 pericarditis without congenital cardiopathy admitted in our pediatric cardiology unit between 1979 and 1994, 19 were purulent. The mean age of these 13 boys and six girls was 3 years (range: 3 months to 10 years). Symptoms always pointed to a chest disease whether pericarditis occurred first (n = 13) or it complicated evolution of a known infectious process (n = 6). Tamponnade was present in seven infants upon admission and required urgent pericardiocentesis or drainage. An extrapericardial infectious site was found in 11 cases: six pulmonary infections, three osteomyelitis, one cellulitis and one sinusitis. An organism was isolated in 17 cases, 14 times in the pericardial fluid, eight times on blood culture. The identified bacteria were: Staphylococcus aureus (n = 6), Haemophilus influenzae (n = 4), Streptococcus A (n = 3), Streptococcus pneumoniae (n = 3), Meningococcus (n = 1). Treatment consisted of intra-venous antibiotics associated 15 times to surgical drainage of the pericardium. One infant had no pericardiocentesis and no drainage because he presented late with constrictive pericarditis and needed pericardectomy. All infants healed but four developed contrictive pericarditis and required pericardectomy; none of these four patients had early drainage (two had no drainage at all). Pericardectomy, carried out between 2 and 6 months after the beginning of pericarditis with adiastolic signs and pericardial thickening, permitted healing in all cases and disappearance of all cardiac symptoms. CONCLUSIONS: Early diagnosis and treatment of purulent pericarditis, especially early pericardial drainage, are the best ways of avoiding constriction.

[Inhaled nitric oxide: a physiologic treatment of persistent pulmonary arterial hypertension in the newborn]. / Le monoxyde d'azote inhalé: un traitement plus physiologique de l'hypertension artérielle pulmonaire persistante du nouveau-né.

Fetal pulmonary circulation is characterized by high resistance and low pulmonary blood flow. Right-to-left shunting through the foramen ovale and/or patent ductus arteriosus is necessary to perfuse the placenta and insure fetal life. At birth, pulmonary arterial blood flow increases immediately by 8- to 10-fold, and allows pulmonary gas exchange and postnatal life. In some circumstances, this adaptation to extra-uterine life is inadequate, because of persistent high pulmonary resistance (PPHN). Due to the lack of a selective pulmonary vasodilator, the treatment of this syndrome remained purely symptomatic using high oxygen levels and barotraumatic mechanical hyperventilation. When this medical treatment failed, the only alternative was extracorporeal membrane oxygenation (ECMO). The discovery of the major role of various endothelium-derived factors including nitric oxide (NO) in the control of vascular reactivity led to dramatic switches in the concepts of severe neonatal respiratory failure and the therapeutic approach of PPHN. It was shown, first in experimental animals then in a few infants with hypoxemic respiratory failure, that NO inhalation selectively vasodilated the vasoconstricted pulmonary vessels, and reversed right-to-left shunting and refractory hypoxemia. Whether inhaled NO also reduces mortality and/or morbidity in hypoxic infants remains to be proven by appropriate randomized clinical trials. However, not only PPHN is associated with pulmonary diseases of various etiologies and underlying pathophysiologic mechanisms, but also inhaled NO is used in conjunction with other validated therapeutic strategies including ante- or postnatal steroids, exogenous surfactants, and high-frequency oscillatory ventilation. Thus, the relevant primary endpoint might be not only crude survival but the most physiological and economical way of obtaining it.

[Congenital diaphragmatic hernia. I. Simple defect of the diaphragm or anomaly of the pulmonary mesenchyme?]. / La hernie diaphragmatique congénitale. I. Simple défect du diaphragme ou pathologie du mésenchyme pulmonaire?

Described for the first time in 1848 by Bochdalek, congenital diaphragmatic hernia is still a hot topic. How can it be that a simple defect of the diaphragm still has a mortality rate reaching 50% in 1997, and this despite continuous progress in neonatal intensive care? If some problems remain unsolved, experimental studies over the past 30 years have raised some questions concerning the pathogenesis, and have shed some light into the pathophysiology of congenital diaphragmatic hernia. This article reviews the recent knowledge about the aetiology, pathogenesis and pathophysiology of this complex malformation.

[Congenital diaphragmatic hernia. II. Is pulmonary hypoplasia an indefinable obstacle?]. / Hernie diaphragmatique congénitale II. L'hypoplasie pulmonaire, obstacle incontournable?

Despite major insights into the pathogenesis and pathophysiology of congenital diaphragmatic hernia, and despite the availability of an antenatal diagnosis and continuous progress in neonatal intensive care, little improvement has been obtained in the prognosis of this malformation. Thus obstetricians, neonatologists and pediatric surgeons are still facing a several dilemma: dilemma before birth to predict the prognosis, i.e., to evaluate the severity of the associated pulmonary hypoplasia in order to decide whether or not to interrupt pregnancy; dilemma after birth in case of severe respiratory failure to decide how far to go in life support. Based on a review of the literature and their own experience, the authors attempt to recapitulate the perinatal management and outcome of this severe malformation.

[Effect of perinatal inflammation syndrome on lung maturation and development]. / Conséquences sur la maturation et le développement pulmonaires du syndrome inflammatoire périnatal.

Despite improvement in neonatal care, the incidence of bronchopulmonary dysplasia has not decreased over the last decade. Moreover, chronic lung disease still occurs in very premature infants who do not require ventilatory support at birth. This review presents the growing body of epidemiological, experimental and clinical evidence suggesting that the occurrence of an inflammatory reaction triggered in utero or immediately after birth is associated with the subsequent development of chronic lung disease. However, stimulators of inflammation or specific proinflammatory cytokines may also have beneficial on lung maturation. How proinflammatory mediators interfere with lung maturation and alveolarization needs to be better understood in order to pave the way for new immunomodulatory strategies to prevent chronic lung disease in very preterm infants.

Understanding and treating pulmonary hypertension in congenital diaphragmatic hernia.

Lung hypoplasia and pulmonary hypertension are classical features of congenital diaphragmatic hernia (CDH) and represent the main determinants of survival. The mechanisms leading to pulmonary hypertension in this malformation are still poorly understood, but may combine altered vasoreactivity, pulmonary artery remodeling, and a hypoplastic pulmonary vascular bed. Efforts have been directed at correcting the "reversible" component of pulmonary hypertension of CDH. However, pulmonary hypertension in CDH is often refractory to pulmonary vasodilators. A new emerging pattern of late (months after birth) and chronic (months to years after birth) pulmonary hypertension are described in CDH survivors. The true incidence and implications for outcome and management need to be confirmed by follow-up studies from referral centers with high patient output. In order to develop more efficient strategies to treat pulmonary hypertension and improve survival in most severe cases, the ultimate therapeutic goal would be to promote lung and vascular growth.

Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury.

Despite substantial progress, mortality and morbidity of the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), remain unacceptably high. There is no effective treatment for ARDS/ALI. The renin-angiotensin system (RAS) through Angiotensin-converting enzyme (ACE)-generated Angiotensin II contributes to lung injury. ACE2, a recently discovered ACE homologue, acts as a negative regulator of the RAS and counterbalances the function of ACE. We hypothesized that ACE2 prevents Bleomycin (BLM)-induced lung injury. Fourteen to 16-week-old ACE2 knockout mice-male (ACE2(-/y)) and female (ACE2(-/-))-and age-matched wild-type (WT) male mice received intratracheal BLM (1.5U/kg). Male ACE2(-/y) BLM injured mice exhibited poorer exercise capacity, worse lung function and exacerbated lung fibrosis and collagen deposition compared with WT. These changes were associated with increased expression of the profibrotic genes α-smooth muscle actin (α-SMA) and Transforming Growth Factor ß1. Compared with ACE2(-/y) exposed to BLM, ACE2(-/-) exhibited better lung function and architecture and decreased collagen deposition. Treatment with intraperitoneal recombinant human (rh) ACE2 (2 mg/kg) for 21 days improved survival, exercise capacity, and lung function and decreased lung inflammation and fibrosis in male BLM-WT mice. Female BLM WT mice had mild fibrosis and displayed a possible compensatory upregulation of the AT2 receptor. We conclude that ACE2 gene deletion worsens BLM-induced lung injury and more so in males than females. Conversely, ACE2 protects against BLM-induced fibrosis. rhACE2 may have therapeutic potential to attenuate respiratory morbidity in ALI/ARDS.

[Lung development and mesenchymal stem cells]. / Développement pulmonaire et cellules souches mésenchymateuses.

The survival of extremely premature newborns has increased because of improvements in perinatal care. These infants however, are at high risk for chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD). BPD, the most common complication in infants born before 28 weeks of gestation, is a multifactorial disease characterized by an arrest in alveolar development. Current preventive and curative therapies show limited efficacy. Cell-based therapies hold tremendous promise in regenerative medicine. Recent evidence suggests the therapeutic benefit of mesenchymal stem (or stromal) cells (MSC) in various diseases, including among others neurodegenerative, cardiovascular and respiratory disorders. Moreover, in an oxygen-induced BPD model, we and others recently demonstrated that bone marrow (BM) derived-MSCs efficiently prevent the arrest in lung development. In this review, we summarize the current knowledge regarding the therapeutic properties and mechanisms of action, specifically paracrine, of MSCs.