Researchers at Cincinnati Children’s Hospital Medical Center have proposed a new method of treating bronchopulmonary dysplasia (BPD) which could help premature babies breathe more easily.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects newborn babies, and mostly premature babies. The condition is caused from damage to the lungs as a result of mechanical ventilation with a respirator and long-term use of oxygen. While a full recovery is possible, BPD may result in life-long breathing difficulties and can be fatal.
The potential new treatment is a form of cell-based therapy that could help stimulate lung development in premature infants with BPD. The potential new therapy was proposed following a study of donated neonatal lung tissue. A single-cell RNA sequencing analysis was performed along with an extensive range of tests on a BPD mouse model.
The researchers discovered c-KIT endothelial progenitor cells were common in embryonic and neonatal lung tissue and help with the formation of alveoli – the air sacs in the lungs essential for gas exchange – but were lower in infants with BPD. Premature babies have underdeveloped lungs and require mechanical breathing assistance, and that interferes with the early development of the lungs.
“RNA sequencing of human and mouse neonatal lung tissue showed that pulmonary c-KIT endothelial progenitor cells require the c-KIT and FOXF1 proteins to stimulate the development of blood vessels and air sacs,” said Vlad Kalinichenko, MD, PhD, lead researcher for the study. “The cells are highly sensitive to injury by high oxygen concentrations, so lung development in premature babies on mechanical oxygen assistance is impeded.
The researchers infused c-KIT-positive endothelial progenitor cells in peripheral blood in neonatal mice that had been exposed to hyperpoxia to model BPD. Mice that had the progenitor cell infusion had higher levels of pulmonary blood vessels and air sacs than the control group.
The researchers suggest that c-KIT-positive endothelial cells could be taken from donors or could be generated from iPSCs derived from the patient’s own cells and could be used as a novel new treatment for BPD that could speed recovery and prevent lifelong breathing problems.
First, the researchers must conduct preclinical testing in rats and sheep before the treatment could be considered for a clinical trail on humans. Kalinichenko believes it will be around two to three years before the treatment could be considered for a human clinical trial.
Further information can be found in the paper – Postnatal Alveologenesis Depends on FOXF1 Signaling in c-KIT Endothelial Progenitor Cells – which was recently published in the American Journal of Respiratory and Critical Care Medicine. DOI: 10.1164/rccm.201812-2312OC