Regular articleThe promise of stem cells in bronchopulmonary dysplasia
Introduction
With advances in perinatal care, prematurely born infants are now capable of being delivered as early as 23–24 weeks of gestation. However, this has made the task increasingly challenging in protecting the extremely immature lung from injury. According to a publication by the World Health Organization, preterm birth affects approximately 10.6% of all births in North America.1 Although there has been a shift in the improvement of survival of these prematurely born infants, there has been no decrease in morbidity. In particular, rates of bronchopulmonary dysplasia (BPD) have not dramatically changed over recent years.2 Recent evidence shows that BPD has long-term respiratory complications, which reach beyond childhood and into adult life, with follow-up studies demonstrating increased risk of respiratory symptoms (i.e. cough and wheeze), poor lung function, and low exercise capacity.3., 4., 5., 6., 7. However, currently there is a lack of efficient treatment for BPD. Such a treatment should not only target the repair of lung injury, but also promote normal lung growth. In doing so, long-term lung function and respiratory health in prematurely born infants could improve. Exciting discoveries in stem/progenitor cell biology over recent years may offer new insight into the pathogenesis of BPD and, more importantly, open new therapeutic avenues.
Section snippets
Current understanding of lung stem cell biology
Stem cells are primitive cells capable of extensive self-renewal with the potential to give rise to multiple differentiated cellular phenotypes.8 Not only are they critical for organogenesis and growth during the early stages of development, but they also contribute to organ repair and regeneration throughout life. In the lung, several local epithelial cell types function as both differentiated functional cells and transit-amplifying progenitors that proliferate in response to airway or
How far have we come? Progress made over past years
Although there are currently no published clinical trials on the use of stem cells in treating or preventing BPD, significant progress in our understanding of stem cell therapy for BPD has been achieved. Advances in our knowledge in this field of research have arisen from an array of studies that have focused not only on the therapeutic benefit of stem cells in experimental models of BPD, but have also focused on resident lung stem cells in health and disease.
Conclusions
In recent years we have uncovered imperative insights and gained extensive knowledge on the stem cells and the lungs in health and disease, and now their therapeutic potential in regenerative medicine is being harnessed for the treatment of neonatal lung injury. Various types of stem cells have shown benefit in experimental models of neonatal lung injury. Before safe clinical translation of cell-based therapies is warranted, we must broaden our knowledge and understanding in this novel and
References (56)
- et al.
Obstructive lung disease in children with mild to severe BPD
Respir Med
(2010) - et al.
The evolving concept of a stem cell: entity or function?
Cell
(2001) - et al.
Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction
Am J Pathol
(2002) - et al.
Identification of bronchioalveolar stem cells in normal lung and lung cancer
Cell
(2005) - et al.
The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium
Cell Stem Cell
(2009) - et al.
Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium
Am J Pathol
(2004) - et al.
Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection
Cell
(2011) - et al.
Adult lung side population cells have mesenchymal stem cell potential
Cytotherapy
(2008) - et al.
Endothelial progenitor cells, bronchopulmonary dysplasia and other short-term outcomes of extremely preterm birth
Early Hum Dev
(2011) - et al.
The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity
Bull World Health Organ
(2010)
The new bronchopulmonary dysplasia
Curr Opin Pediatr
Bronchopulmonary dysplasia in very low birth weight subjects and lung function in late adolescence
Pediatrics
Evidence of unexpected oxidative stress in airways of adolescents born very preterm
Eur Respir J
Longitudinal evaluation of airway function 21 years after preterm birth
Am J Respir Crit Care Med
Reduced exercise capacity in children born very preterm
Pediatrics
Epithelial stem cells of the lung: privileged few or opportunities for many?
Development
Endogenous fibroblastic progenitor cells in the adult mouse lung are highly enriched in the sca-1 positive cell fraction
Stem Cells
Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung
Proc Natl Acad Sci USA
The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells
Development
Novel stem/progenitor cell population from murine tracheal submucosal gland ducts with multipotent regenerative potential
Stem Cells
Molecular phenotype of airway side population cells
Am J Physiol Lung Cell Mol Physiol
Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion
Am J Respir Cell Mol Biol
Parabronchial smooth muscle constitutes an airway epithelial stem cell niche in the mouse lung after injury
J Clin Invest
Isolation of a putative progenitor subpopulation of alveolar epithelial type 2 cells
Am J Physiol Lung Cell Mol Physiol
Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity
Am J Physiol Lung Cell Mol Physiol
Endogenous lung stem cells: what is their potential for use in regenerative medicine?
Expert Rev Respir Med
Endogenous lung stem cells and contribution to disease
J Pathol
The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen
Lab Invest
Cited by (24)
Oxidative stress and bronchopulmonary dysplasia
2018, GeneCitation Excerpt :Now, bronchopulmonary dysplasia (BPD) incidence is rising year by year. Current research shows that (Carraro et al., 2013; O'Reilly and Thébaud, 2013; Kotecha et al., 2013) although BPD is a multi-factor disease, including premature lung development immature, infection, nutrition, oxygen poisoning, volumetric injury during mechanical ventilation, barotrauma and inflammatory factor response, etc., its main risk factor is due to the exposure to hyperoxia and the role of reactive oxygen species (ROS) on premature infants. Previous studies have shown that children with BPD have a poor prognosis.
Cell-based strategies to reconstitute vital functions in preterm infants with organ failure
2016, Best Practice and Research: Clinical Obstetrics and GynaecologyCitation Excerpt :MSCs are the most extensively examined. The source of the cells may be adult bone marrow, umbilical cord blood, Wharton's jelly, fetal tissue, placenta, or adipose tissue, the first two being the most widely used in neonatal studies [35]. Apart from MSCs, endothelial progenitor cells (EPCs) and amnion epithelial cells (AECs) are the focus of study.
Neonatology for Anesthesiologists
2016, Smith's Anesthesia for Infants and Children, Ninth EditionCord and cord blood-derived endothelial cells
2015, Cord Blood Stem Cells MedicineThe Effects of Neonatal Hyperoxia on Lung Development
2014, The Lung: Development, Aging and the Environment: Second EditionDevelopmental Physiology of the Pulmonary Circulation
2014, The Lung: Development, Aging and the Environment: Second Edition