Scientists from the Columbia University Medical Center say they have succeeded in transforming human stem cells into functional lung and airway cells. The researchers add that this development has significant potential for modeling lung disease, screening drugs, studying human lung development, and, ultimately, generating lung tissue for transplantation. The study (“Highly efficient generation of airway and lung epithelial cells from human pluripotent stem cells”) was published in Nature Biotechnology.
“Researchers have had relative success in turning human stem cells into heart cells, pancreatic beta cells, intestinal cells, liver cells, and nerve cells, raising all sorts of possibilities for regenerative medicine,” said study leader Hans-Willem Snoeck, M.D., Ph.D., professor of medicine and affiliated with the Columbia Center for Translational Immunology and the Columbia Stem Cell Initiative. “Now, we are finally able to make lung and airway cells. This is important because lung transplants have a particularly poor prognosis. Although any clinical application is still many years away, we can begin thinking about making autologous lung transplants—that is, transplants that use a patient's own skin cells to generate functional lung tissue.”
The research builds on Dr. Snoeck's 2011 discovery of a set of chemical factors that can turn human embryonic stem (ES) cells or human induced pluripotent stem (iPS) cells into anterior foregut endoderm, the precursors of lung and airway cells. In the current study, Dr. Snoeck and his colleagues found new factors that can complete the transformation of human ES or iPS cells into functional lung epithelial cells. The resultant cells were found to express markers of at least six types of lung and airway epithelial cells, particularly markers of type 2 alveolar epithelial cells, which participate in repair of the lung after injury and damage.
“We have established, based on developmental paradigms, a highly efficient method for directed differentiation of hPSCs into lung and airway epithelial cells. Long-term differentiation of hPSCs in vivo and in vitro yielded basal, goblet, Clara, ciliated, type I and type II alveolar epithelial cells,” wrote the investigators. “The type II alveolar epithelial cells were capable of surfactant protein-B uptake and stimulated surfactant release, providing evidence of specific function. Inhibiting or removing retinoic acid, Wnt, and BMP—agonists to signaling pathways critical for early lung development in the mouse—recapitulated defects in corresponding genetic mouse knockouts.”
The findings have implications for the study of a number of lung diseases including idiopathic pulmonary fibrosis (IPF), in which type 2 alveolar epithelial cells are thought to play a central role. “No one knows what causes the disease, and there's no way to treat it,” says Dr. Snoeck. “Using this technology, researchers will finally be able to create laboratory models of IPF, study the disease at the molecular level, and screen drugs for possible treatments or cures.”
Dr. Snoeck also hopes this technology will eventually be used to make an autologous lung graft.
“This would entail taking a lung from a donor; removing all the lung cells, leaving only the lung scaffold; and seeding the scaffold with new lung cells derived from the patient,” he explained. “In this way, rejection problems could be avoided.”