Researchers at Columbia University have become the first to successfully bioengineer a functional vascularized lung scaffold to treat disease.
The scaffold allows the removal of the pulmonary epithelium while maintaining the viability and function of the vascular network and the lung matrix.
The study, published today in Science Advances, aimed to overcome the issue of finding new ways to promote lung repair and increase the number of donor lungs to treat end-stage lung disease.
End-stage lung disease is the third leading cause of death worldwide, accounting for 400,000 deaths per year in the United States alone.
The lung has more than 40 different types of cells and the total surface area between the airway and the vasculature is about the size of a tennis court, making previous efforts to bioengineer functional lungs from fully decelluarized or synthetic scaffolds that lack functional vasculature more difficult.
The team at Columbia University report they are the first to successfully bioengineer a functional lung with perfusable and healthy vasculature in an ex vivo rodent lung. The approach allows for the removal of pulmonary epithelium while still maintaining the viability and function of the vascular network and lung matrix.
“We developed a radically new approach to bioengineering of the lung,” Gordana Vunjak-Novakovic, a pioneer in tissue engineering who directs the Laboratory for Stem Cells and Tissue Engineering at Columbia, said in a press release.
“We reasoned that an ideal lung scaffold would need to have perfusable and healthy vasculature, and so we developed a method that maintains fully functional lung vasculature while we remove defective epithelial lining of the airways and replace it with healthy therapeutic cells. This ability to selectively treat the pulmonary epithelium is important, as most lung conditions are diseases of the epithelium.”
Researchers developed an airway-specific method to remove the pulmonary epithelium while still preserving the lung vasculature, matrix and other supporting cell types such as fibroblasts, myocytes, chondrocytes and pericytes.
They ventilated the lungs following lung cannulation in a rodent lung and perfused them on an ex vivo lung perfusion system, or EVLP. Researchers then used a mild detergent solution to remove epithelial cells, while protecting the vasculature by circulating a perfusate containing electrolytes and energy substrates at the same time.
“This is a major step forward in bioengineering lungs,” Vunjak-Novakovic said. “The creation of de-epithelialized whole lungs with functional vasculature may open new frontiers in lung bioengineering and regenerative medicine. This project could not have been successfully completed without the interdisciplinary effort that made us step out from our zone of comfort, and try novel approaches in collaboration with bioengineers, clinical scientists, and stem cell scientists.”
By Amy Wallace