As of 2017, about 1 in 10 babies are born prematurely in the United States, and as a result, one major concern rings in physicians’ minds: respiratory complications. Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity (1). BPD is a form of chronic lung disease resulting from disrupted alveolar growth that affects newborns (mostly premature) and infants. It results from damage to the lungs caused by mechanical ventilation (respirator) and long-term use of oxygen. Most infants recover from BPD, but some may have long-term breathing difficulty, and in most severe cases– lifelong breathing problems and even death (2).
Most recently, researchers have suggested a possible cell-based therapy to stimulate lung development in premature infants who suffer from Bronchopulmonary Dysplasia (BPD). As reported in the American Journal of Respiratory and Critical Care Medicine, scientists have been studying genetic signatures in donated human neonatal lungs via single-cell RNA sequencing analysis and also performed extensive laboratory tests on mouse models of BPD, including computer-assisted bioinformatics analysis (3).
The tests led to a proposal to develop cell therapy based on what are called c-KIT endothelial progenitor cells, which are common in embryonic and neonatal lungs and help in the formation of capillaries and air sacs in the lungs (alveoli). But premature babies with already underdeveloped lungs frequently rely on mechanical breathing assistance, which further interferes with early lung development by loss of pulmonary microvasculature, according to leady investigator Vlad Kalinichenko, MD, PhD, a physician/researcher at the Cincinnati Children's Perinatal Institute's Center for Lung Regenerative Medicine (3).
This study is the first to suggest the possibility of using donated c-KIT pulmonary endothelial progenitor cells for therapy or those generated with pluripotent stem cells, which can become any cell type in the body and be derived from a patient's own cells. That conclusion was based in part on tests the researchers performed by using c-KIT-positive endothelial progenitor cells to treat neonatal mice that had been exposed to hyperpoxia (over oxygenation) to model the BPD condition in the animals. They found that the infusion of cells in peripheral blood increased the formation of pulmonary blood vessels and air sacs in the animals (3, 4).
Additionally, further research has attempted to tackle preventative strategies in combating BPD early on. One of the main goals in BPD research is the early prediction of very low birth weight infants who are at risk of developing BPD in order to initiate adequate preventive strategies (5). Other benefits of determining the risk of BPD include providing prognostic information and stratifying infants for clinical trial enrollment. Furthermore, researchers hope to address BPD's complex pathophysiology by identifying prognostic biomarkers and developing novel in vitro human lung models in order to develop effective therapies by taking advantage of recent scientific progress in -omics, 3D organoids, and regenerative medicine (5).
This research holds great potential impact for the future of neonatal care and future clinical testing will shed light on the continued need for intensive BPD management, allowing scientists to lend their results to the amelioration of other cardiac, pulmonary, and congenital conditions.