A revolutionary new process 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.
The process, 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.
It enables researchers—for the first time—to capture airway stem cells from patients, replicate them in the lab, and then use these strains of cells to observe the progression of disease and test potential treatments.
In addition to airway cells, the protocol also appears to work for adult 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,” Rajagopal says. “We hope it changes the way people study skin and esophageal diseases as well.”
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, or making another copy of themselves.
The newly replicated cells then mature into the specialized cell types they are genetically programmed to become. An airway stem cell will turn into a mature airway cell, for example, and a skin stem cell will turn into a skin cell. Once the cell has changed into its mature form, it loses the ability to replicate.
Before the Rajagopal lab team’s discovery, the tendency of these cells to mature and stop replicating posed a challenge for researchers hoping to cultivate large samples of airway tissue in the lab.
Because the cells stop replicating once they mature, the only stem cell tissues that scientists could test and observe were those they could gather directly from patients.
However, these tissue samples were typically not large enough to support testing multiple treatments on the same cells.
In their new Cell Stem Cell paper, Rajagopal and his team describe an easy protocol for creating a chemical solution that stops the signals that prompt adult stem cells to change into their final form.
As long as they are kept in this chemical solution, the cells they stay in their immature form and reproduce over and over again, creating a large pool of genetically identical cells.
Once they are taken out of the solution, they turn into their final form (i.e. functioning airway cells), and scientists can then observe how they are affected by different airway diseases, or use the cells to test treatment options.
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, Rajagopal says.
“We’re experts on the lung and we think we can make pretty good lung cells,” Rajagopal says. “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 the new protocol, he says this is just the first step in a long process of discovery.
“There is no magic bullet in science, no one procedure that solves everything,” he notes. “There are always more and more steps to take. We need a lot of scientists working on this.”
Brian Burns 