A revolutionary new method for growing adult stem cells outside the body may help to unlock the mysteries behind lung diseases such as cystic fibrosis, chronic obstructive pulmonary disorder, asthma and lung cancer.

This protocol, which was developed in the lab of Jay Rajagopal, MD, at Massachusetts General Hospital, is detailed in the August 2016 issue of Cell Stem Cell. Rajagopal is an investigator in the Center of Regenerative Medicine at Mass General and the Kevin and Polly Maroni MGH Research Scholar.

The protocol enables researchers—for the first time—to capture airway cells from patients, expand them in the lab, and then use these cells to observe the progression of disease and test potential treatments. The process also appears to work for stem cells from other organs and tissues in the body, including the skin and the esophagus.

“We are very excited about the publication of this paper because we think it is going to change the way we study lung disease. We hope it changes the way people study skin and esophageal disease as well,” Dr. Rajagopal said in a recent interview.

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Rajagopal explained that many organs and tissues in the body—such as those of the airway, the esophagus and the skin, are created and maintained by adult epithelial stem cells.

When an organ or tissue is damaged by disease, or by the normal wear and tear of living, these adult stem cells repair the damage by replicating. The newly replicated cells then turn into the specialized cell types they are genetically designed to become.

An airway stem cell will turn into an airway cell, for example, and a skin stem cell will turn into a skin cell. Once a stem cell has changed into its mature form, it loses the ability to replicate.

Before Rajagopal’s discovery, this posed a challenge for researchers hoping to cultivate large samples of human airway tissue in the lab. Because the cells stop replicating once they reach their final form, the only tissues that scientists could test and observe were those that they could gather directly from a patient.

These tissue samples were typically not large enough to support testing multiple treatments on the same cells, so researchers always had to account for genetic differences between cells when trying to determine if a treatment worked.

In their new Cell Stem Cell paper, Rajagopal and his team outline an easy protocol for creating a chemical solution that stops the signaling process that prompts the stem cells to mature. With that signal inhibited, the cells stay in an immature form and continue to replicate, creating genetically identical copies over multiple generations.

This makes it possible to grow large cultures of identical cells that can be used for testing treatments and observing the progression of disease.When researchers want to convert the cells into mature airway cells, they simply remove them from the inhibitory solution and let nature take its course.

The team first tried the process on human adult airway stem cells that were captured from the coughs of patients with cystic fibrosis. Once placed in the solution, the stem cells continued to replicate many times over without differentiating. Upon examination, the new cells proved to be of comparable quality to the originals.

“We’re experts on the lung and we think we can make pretty good lung cells,” Rajagopal said. “They are not perfect, and if you expand them long enough they’ll start deteriorating, but we are figuring out how to fix that problem.”

The team has used the same process to replicate other adult epithelial stem cells captured from the body—such as those in the skin and esophagus—and the results have been similarly encouraging. The next step will be for the scientific experts in those areas to examine the cells more closely.

While Rajagopal is optimistic about the potential of this discovery, he says this is just the first step in a very long process of discovery. By sharing this protocol, the team hopes to prompt many new avenues of scientific inquiry.

“There is no magic bullet in science; no one procedure solves everything,” he noted. “There are always more steps to take. We need a lot of scientists working on this.”


Research at Mass General

Research at Massachusetts General Hospital

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