New Stem Cell Culturing Technique Shows Promise for COPD, Asthma

Taking tissue samples collected during routine treatments of lung disorders to generate and expand airway stem cells could improve stem cell therapies, a recent study suggests.

The study, published in Cell Stem Cell, primarily focused on a cellular signaling pathway that regulates cell growth and the process of differentiation. Proteins such as TGF-β and bone morphogenic protein (BMP) activates the pathway causing it to send signals to the nucleus through intracellular proteins called SMADs.

Researchers sought to determine whether inhibiting SMAD pathways could foster the expansion of cultured adult stem cells by preventing differentiation.

“This new methodology opens up new avenues for research in any airway disease, such as asthma or COPD,” said senior study author Jayaraj Rajagopal, MD. “While in the past we could only expand stem cells for a few generations, now we have the ability to generate enough cells to last multiple laboratories for years of experiments. Our system is also very simple, avoiding the complexities of former culture systems and making it more accessible to many labs.”

For the study, researchers conducted a series of experiments. During the first, they were able to confirm TGF-β/BMP and SMAD signaling were active in differentiated cells and inactive in adult stem cells. When they blocked the SMAD signaling, it prevented the differentiation of airway stem cells from mice, while blocking both TGF-β and BMP pathways allowed for the expansion of numerous generations of airway stem cells.

When this approach was used on samples taken during a bronchoscopy, researchers were able to generate human airway stem cells. Furthermore, they were able to successfully generate and maintain the airway stem cells from samples of the sputum.

“If we could find ways to induce cough samples containing larger numbers of stem cells, our technique would represent the least invasive way to obtain any stem cell from any organ, and if we could improve the procedure to yield stem cell cultures from 100% of sputum samples, we could acquire samples to study lung disease in the laboratory with less invasiveness than a blood draw,” Rajagopal said.

This approach could be performed on other tissues if scientists are able to grow the stem cells from acquired samples.

“We also found that the same methodology works for many tissues of the body — from the skin to the esophagus to mammary glands,” Rajagopal said. “Many of these organ tissues cannot currently be cultured, so it remains to be seen whether scientists in these areas will be able to grow stem cells from samples acquired from other minimally invasive procedures, including the collection of secretions. If all this becomes possible, it would represent a big step forward for personalized medical approaches to disease. In many diseases, lung diseases in particular, the mouse is a very poor model of human disease, so this ability really opens up new horizons to apply human genetics to human lung cells and disease models.”

Although this approach proved to be successful in maintaining adult stem cell function through many generations, they did eventually start to deteriorate. Researchers noted that their next goal is to reduce or try to eliminate the function loss of adult stem cells.

“We have lots of ideas and collaborations in place to try and sort out ways to make these cells nearly perfect,” Rajagopal said. “The problem may be genetic or epigenetic, and the MGH (Massachusetts General Hospital) has considerable expertise in both of these areas of investigation.”