Boston scientists grow lung tissue from cystic fibrosis patients’ skin cells

By JoanneRUSSELL25

By Carolyn Y. Johnson, Globe Staff

Two teams of Boston scientists have developed new ways to turn stem cells into different types of lung tissue, surmounting a major hurdle for scientists trying to harness the power of stem cell biology to study and develop treatments for major lung diseases.

One team then used skin cells from cystic fibrosis patients to create embryonic-like stem cells, then working in lab dishes used those cells to grow tissue that lines the airways and contains a defect responsible for the rare, fatal disease. The technique -- essentially a recipe for growing such lung tissue -- could provide a powerful platform to screen drugs and study the biology of the disease.

Growing lung tissue in the laboratory has long been a goal of stem cell scientists, but has been more technically difficult than growing other types of tissues, such as brain cells or heart cells. Such lung tissue is valuable because it could be used to screen potential drugs and more closely probe the problems that underlie diseases such as asthma, emphysema, and rare genetic diseases. Such techniques may also one day help researchers grow replacement tissues and devise ways to restore or repair injured lung tissue.

A team led by Massachusetts General Hospital researchers created lung tissue from a patient with the genetic mutation that most commonly underlies cystic fibrosis and researchers hope the technique will also be a powerful tool to study other diseases that affect the airway tissue, such as asthma and lung cancer. The other team, led by Boston University School of Medicine scientists, was able to derive cells that form the delicate air sacs of the lung from mouse embryonic stem cells. The team is hoping to refine the recipe for making the cells so that they can be used to derive lung tissue from a bank of 100 stem cell lines of patients with lung disease. Both papers were published Thursday in the journal Cell Stem Cell.

Vertex Pharmaceuticals, a Cambridge biotechnology company, earlier this year received approval for Kalydeco -- the first drug to directly target the underlying cause of cystic fibrosis. That compound was discovered by screening massive numbers of potential drugs against cells engineered to carry the same defect that underlies cystic fibrosis.

We had to use engineered cells, and certainly using more native human cells ... would be potentially beneficial, said Dr. Frederick Van Goor, head of biology for Vertexs cystic fibrosis research program. We had to rely on donor tissue obtained from patients with cystic fibrosis, and its a bit more challenging, because the number of donor lungs you can get and the number of cells you can derive from there are more limited.

Van Goor said it was too soon to say whether the company would use the new technology in screening, but noted that the tests the company had used to determine whether a drug was likely to work against the disease had, in some cases, given scientists false leads. Some molecules that worked on the engineered cells did not work in the complicated biology of the lung.

Its a significant event for the lung field, said Dr. Thiennu Vu, associate professor of medicine at the University of California San Francisco, who was not involved in the research. She added that much work remains before such cells could be used to repair or replace damaged tissue, and even before such cells would necessarily be useful for drug screening. It will be important, she said, to refine the recipe to ensure that the technique yields pure populations of the specific types of functional lung cells.

In the competitive world of science, where credit for being the first to do something is crucially important, the two research teams accomplishments are an unusual example of competitors turning into collaborators -- forging a relationship that both teams felt helped speed up progress.

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Boston scientists grow lung tissue from cystic fibrosis patients’ skin cells

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