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"In the longer term, we hope to use this technology to make an autologous lung graft," says Hans-Willem Snoeck. "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. In this way, rejection problems could be avoided." (Credit: iStockphoto)

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Scientists make lung cells from human stem cells

Scientists have finally turned human stem cells into functioning lung cells, and say the breakthrough paves the way for using a patient’s own cells for lung transplant.

“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,” says study leader Hans-Willem Snoeck, professor of medicine at Columbia University. “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.”

Human embryonic stem cells differentiated into type II alveolar lung epithelial cells (green). (Credit: Sarah Xuelian Huang/Columbia Center for Translational Immunology)
Human embryonic stem cells differentiated into type II alveolar lung epithelial cells (green). (Credit: Sarah Xuelian Huang/Columbia Center for Translational Immunology)

Complete the transformation

The research builds on 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—precursors of lung and airway cells.

Human iPS cells closely resemble human ES cells but are generated from skin cells, by coaxing them into taking a developmental step backwards. Human iPS cells can then be stimulated to differentiate into specialized cells—offering researchers an alternative to human ES cells.

In the current study, published in the journal Nature Biotechnology, Snoeck and colleagues found new factors that can complete the transformation of human ES or iPS cells into functional lung epithelial cells—cells that cover the lung surface.

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. Type 2 cells are important because they produce surfactant, a substance critical to maintain the lung alveoli, where gas exchange takes place; they also participate in repair of the lung after injury and damage.

New drugs and transplants

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 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.”

“In the longer term, we hope to use this technology to make an autologous lung graft,” Snoeck adds. “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. In this way, rejection problems could be avoided.”

Columbia University has filed for a patent relating to the generation of lung and airway epithelium from human pluripotent stem cells and uses thereof. The authors declare no other financial or other conflicts of interests.

Funds from Columbia University and the New York Stem Cell Foundation supported the work.

Source: Columbia University

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