U of Pitt Team Discovers Stem Cells in the Esophagus

Even though several studies have been unsuccessful at identifying a stem population in the esophagus, a study from the University of Pittsburgh has discovered a stem cell pool that services the esophagus. Researchers from the University of Pittsburgh School of Medicine have published an animal report in the journal Cell Reports that might lead to new insights into the development and treatment of esophageal cancer and a precancerous condition known as Barrett’s esophagus.

In the US, more than 18,000 people will be diagnosed with esophageal cancer in 2014 and almost 15,500 people will die from it, according to numbers generated by the American Cancer Society. The precancerous condition known as Barrett’s esophagus is characterized by tissue changes in the lining of the esophagus in which the esophageal lining begins to resemble the tissue architecture of the intestine. Barrett’s esophagus is usually a long-term consequence of gastro-esophageal reflux disease or GERD.

“The esophageal lining must renew regularly as cells slough off into the gastrointestinal tract,” said senior investigator Eric Lagasse, Pharm.D., Ph.D., associate professor of pathology, Pitt School of Medicine, and director of the Cancer Stem Cell Center at the McGowan Institute for Regenerative Medicine. “To do that, cells in the deeper layers of the esophagus divide about twice a week to produce daughter cells that become the specialized cells of the lining. Until now, we haven’t been able to determine whether all the cells in the deeper layers are the same or if there is a subpopulation of stem cells there.”

Lagasse and his team grew small explants of esophageal tissue in culture. These esophageal “organoids” from mice were then used to conduct experiments that were used to identify and track the different cells in the basal layer of the tissue. In these organoids, Lagasse and others found a small population of cells that divide more slowly, are less mature, can differentiate into several different types of esophageal-specific cell types, and have the ability to self-renew. The ability to self-renew is a defining feature of stem cells.

“It was thought that there were no stem cells in the esophagus because all the cells were dividing rather than resting or quiescent, which is more typical of stem cells,” Dr. Lagasse noted. “Our findings reveal that there indeed are esophageal stem cells, and rather than being quiescent, they divide slowly compared to the rest of the deeper layer cells.”

Lagasse and his team would now like to examine human esophageal tissues from patients with Barrett’s esophagus in order to determine if such patients show evidence of esophageal stem cell dysfunction.

“Some scientists have speculated that abnormalities of esophageal stem cells could be the origin of the tissue changes that occur in Barrett’s disease,” Dr. Lagasse said. “Our current and future studies could make it possible to test this long-standing hypothesis.”