BPD

Preterm birth is the leading cause of death in newborns and children. Despite advances in perinatology, immature infants continue to face serious risks such chronic respiratory impairment from bronchopulmonary dysplasia (BPD). Current treatment options are insufficient and novel approaches are desperately needed. In recent years stem cells have emerged as potential candidates to treat BPD with mesenchymal stem/stromal cells (MSCs) being particularly promising. MSCs originate from several stem cell niches including bone marrow, skin, or adipose, umbilical cord, and placental tissues...

The field of stem cell biology, cell therapy, and regenerative medicine has expanded almost exponentially, in the last decade. Clinical trials are evaluating the potential therapeutic use of stem cells in many adult and pediatric lung diseases with vascular component, such as bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), or pulmonary arterial hypertension (PAH). Extensive research activity is exploring the lung resident and circulating progenitor cells and their contribution to vascular complications of chronic lung diseases, and researchers hope to use resident or circulating stem/progenitor cells to treat chronic lung diseases and their vascular complications...

Bronchopulmonary dysplasia (BPD), a chronic lung disease affecting very premature infants, is a major cause of mortality and long-term morbidities despite of current progress in neonatal intensive care medicine. Though there has not been any effective treatment or preventive strategy for BPD, recent stem cell research seems to support the assumption that stem cell therapy could be a promising and novel therapeutic modality for attenuating BPD severity. This review summarizes the recent advances in stem cell research for treating BPD...

RATIONALE: While infants who are born extremely premature and develop bronchopulmonary dysplasia (BPD) have impaired alveolar development and decreased pulmonary diffusion (DLCO), it remains unclear whether infants born less premature and do not develop BPD, healthy premature (HP), have impaired parenchymal development. In addition, there is increasing evidence that pro-angiogenic cells are important for vascular development; however, there is little information on the relationship of pro-angiogenic cells to lung growth and development in infants...

Despite great achievements in neonatal and perinatal medicine over the past decades, the immature lung remains the most critical organ to care for after premature birth. As a consequence, bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity. BPD impairs normal development and may cause lifelong morbidities. At present, there is no effective treatment for BPD - including preventing premature birth. Recent insights into the biology of stem and progenitor cells have ignited the hope of protecting the immature lung, and even regenerating an already damaged lung by using exogenous stem- or progenitor cells as therapeutics...

Bronchopulmonary dysplasia (BPD) is a major cause of substantial lifelong morbidity in preterm infants. Despite a better understanding of the pathophysiology of BPD and significant research effort into its management, there remains today no effective treatment. Cell-based therapy is a novel approach that offers much promise in the prevention and treatment of BPD. Recent research supports a therapeutic role for cell transplantation in the management of a variety of acute and chronic adult and childhood lung diseases, with potential of such therapy to reduce inflammation and prevent acute lung injury...

Bronchopulmonary dysplasia (BPD) is a chronic lung disease with long-term complications that affects mainly preterm born children with low birth weights, especially those treated with mechanical ventilation and oxygen therapy. Successful treatment of BPD could reduce the incidence of other diseases of prematurity such as periventricular leukomalacia and retinopathy. The effects of current therapies are unsatisfactory; thus, searching for novel therapeutic is underway. One promising approach seems administration of mesenchymal stem cells (MSC)...

All adult tissues, including the lung, have some capacity to self-repair or regenerate through the replication and differentiation of stem cells resident within these organs. While lung resident stem cells are an obvious candidate cell therapy for lung diseases, limitations exist regarding our knowledge of the biology of these cells. In contrast, there is considerable interest in the therapeutic potential of exogenous cells, particularly mesenchymal stem/stromal cells (MSCs), for lung diseases. Bone marrow derived-MSCs are the most studied cell therapy for these diseases...

Preterm infants frequently suffer from pulmonary complications resulting in significant morbidity and mortality. Physiological and structural lung immaturity impairs perinatal lung transition to air breathing resulting in respiratory distress. Mechanical ventilation and oxygen supplementation ensure sufficient oxygen supply but enhance inflammatory processes which might lead to the establishment of a chronic lung disease called bronchopulmonary dysplasia (BPD). Current therapeutic options to prevent or treat BPD are limited and have salient side effects, highlighting the need for new therapeutic approaches...

Preterm birth affects approximately 11% of all newborns worldwide and is a major risk factor for infant mortality and morbidity. A common complication of preterm birth is the chronic lung disease of prematurity called bronchopulmonary dysplasia (BPD). Due to the lack of a specific treatment for BPD, preterm infants surviving with BPD face a lifelong risk of poor lung health. The therapeutic potential of stem cells in regenerative medicine is being harnessed for many diseases, including BPD. Compelling preclinical data using stem cells to prevent/repair lung damage in animal models of experimental BPD has built the basis for its translation into the clinic in preterm infants...

Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity resulting in significant morbidity and mortality. The pathology of BPD is multifactorial and leads to alveolar simplification and distal lung injury. Previous studies have shown a beneficial effect of systemic treatment with bone marrow-derived mesenchymal stromal cells (MSCs) and MSC-conditioned media (MSC-CM) leading to amelioration of the lung parenchymal and vascular injury in vivo in the hyperoxia murine model of BPD. It is possible that the beneficial response from the MSCs is at least in part due to activation of endogenous lung epithelial stem cells...

Continuous improvements in perinatal care have allowed the survival of ever more premature infants, making the task of protecting the extremely immature lung from injury increasingly challenging. Premature infants at risk of developing chronic lung disease or bronchopulmonary dysplasia (BPD) are now born at the late canalicular stage of lung development, just when the airways become juxtaposed to the lung vasculature and when gas-exchange becomes possible. Readily available strategies, including improved antenatal management (education, regionalization, steroids, and antibiotics), together with exogenous surfactant and exclusive/early noninvasive ventilatory support, will likely decrease the incidence/severity of BPD over the next few years...

Clinical trials investigating mesenchymal stromal cell (MSC) therapy for bronchopulmonary dysplasia have been initiated; however, the optimal delivery route and functional effects of MSC therapy in newborns remain incompletely established. We studied the morphologic and functional effects of intranasal versus i.p. MSC administration in a rodent model of neonatal lung injury. Cultured human cord tissue MSCs (0.1, 0.5, or 1 × 10(6) cell per pup) were given intranasally or i.p. to newborn severe combined immunodeficiency-beige mice exposed to 90% O2 from birth; sham controls received an equal volume of phosphate-buffered saline...

BACKGROUND: Impairment of endothelial progenitor cells (EPCs) has been shown to contribute to the development of bronchopulmonary dysplasia (BPD). In the current study, the relationship between EPC changes of after birth and the development of BPD was investigated, and the effects of inhaled nitric oxide (iNO) on EPCs were evaluated. METHODS: Sixty infants with a gestational age of less than 32 weeks and a birth weight of less than 1500 g were studied. NO was administered to infants who were receiving mechanical ventilation or CPAP for at least 2 days between the ages of 7 and 21 days...

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity, which affects very preterm infants. Advances in perinatal care have enabled the survival of infants born as early as 23-24 weeks of gestation, but make the task more challenging of protecting injury to an ever more immature lung. Currently, there is no specific treatment for BPD. Recent advances in our understanding of stem/progenitor cells and their potential to repair damaged organs offer the possibility of cell-based treatments for neonatal lung injury...

BACKGROUND: Bronchopulmonary dysplasia is an independent risk factor for adverse neurodevelopmental outcomes in premature infants. We investigated whether attenuation of hyperoxic lung injury with intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells (MSCs) could simultaneously mitigate brain damage in neonatal rats. METHODS: Newborn Sprague-Dawley rats were exposed to hyperoxia or normoxia conditions for 14 d. MSCs (5 × 10(5) cells) were transplanted intratracheally at postnatal day (P) 5...

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a main complication of extreme prematurity and currently lacks efficient treatment. Rat bone marrow-derived mesenchymal stem cells (MSC) prevent lung injury in an oxygen-induced model of BPD. Human cord is an advantageous source of stem cells that is especially appealing for the treatment of neonatal diseases. The therapeutic benefit after established lung injury and long-term safety of cord-derived stem cells is unknown. METHODS: Human cord-derived perivascular cells (PCs) or cord blood-derived MSCs were delivered prophylactically or after established alveolar injury into the airways of newborn rats exposed to hyperoxia, a well-established BPD model...

OBJECTIVE: To assess the safety and feasibility of allogeneic human umbilical cord blood (hUCB)-derived mesenchymal stem cell (MSC) transplantation in preterm infants. STUDY DESIGN: In a phase I dose-escalation trial, we assessed the safety and feasibility of a single, intratracheal transplantation of hUCB-derived MSCs in preterm infants at high risk for bronchopulmonary dysplasia (BPD). The first 3 patients were given a low dose (1 × 10(7) cells/kg) of cells, and the next 6 patients were given a high dose (2 × 10(7) cells/kg)...

Despite remarkable improvements in survival of extremely premature infants, the burden of BPD among survivors remains a frustrating problem for parents and caregivers. Advances, such as antenatal steroids and surfactant replacement, which have dramatically improved survival, have not reduced BPD among survivors. Other advances that have significantly improved the combined outcome of death or BPD, such as vitamin A and avoidance of mechanical ventilation, have had smaller magnitude effects on the outcome of BPD alone...

Although bronchopulmonary dysplasia (BPD) is the most frequent adverse outcome for infants born at < 30 weeks gestational age, there remain major gaps in understanding the pathophysiology, and thus there are few effective targeted therapies to prevent and treat BPD. This review will focus on the substantial problems and knowledge gaps for the clinician and investigator when considering lung injury and BPD. The epidemiology of BPD is clear: BPD is a lung injury syndrome predominantly in extremely low-birth-weight infants with an incidence that increases as gestation/birth weight decrease, with growth restriction, in males and with fetal exposures and with injury from postdelivery respiratory care...