A potential cause of Barrett's esophagus has been found.
A report on the study — which was led by a team from Columbia University Medical Center (CUMC) in New York City, NY, and published in the journal Nature — describes how they used mice and human tissue to pinpoint the "cell of origin" for Barrett's esophagus.
In Barrett's esophagus, some of the tissue that lines the esophagus, or the tube that carries food from the mouth to the stomach, changes into tissue that is more like that which lines the intestines. This can be felt as pyrosis and difficulty swallowing food.
Most cases arise from gastropassage reflux illness (GERD), a degenerative condition in which acid from the stomach regurgitates into the lower part of the food pipe.
In a small proportion of cases, Barrett's esophagus can develop into a rare cancer called passage glandular cancer. Although the cancer is rare, it is the most common form of passage cancer.
Better screening and treatment needed
The incidence of passage glandular cancer has accrued quickly in the United States over recent decades. But unluckily, this has not been matched by improved screening and treatment.
As with other cancers, early detection is the key to prolonging survival in passage cancer. At present, under 20 percentage of patients survive for longer than 5 years after diagnosis.
Scientists inquisitory the origins of Barrett's esophagus have put forward models based on at least five different cell types.
"However," explains study leader Jianwen Que, an associate prof of medicine at CUMC, "none of these experimental models mimics all of the characteristics of the condition."
He and his colleagues believed, therefore, that the "cell of origin" for Barrett's esophagus was still waiting to be discovered.
The gastropassage junction
The researchers started their investigation by breeding mice genetically engineered to develop Barrett's esophagus, and then examining the area where the food pipe joins the stomach. This area, called the gastropassage junction, is where abnormal tissue that is typical of Barrett's oesophagus occurs.
Here, at the gastropassage junction, the tissue that lines the digestive tract, or the epithelial tissue, changes bit by bit — as it nears the stomach — from that of the food pipe to that of the intestines. At this "transformation epithelial tissue," the cell types transition from "stratified squamous epithelial tissue cells" to "simple columnar cells."
Prof. Que explains that, piece the examination discovered that all the "known cells in this tissue remained the same," the team found "a antecedently unidentified zone inhabited by unique basal primogenitor cells."
Progenitor cells are stem cells that have just started to differentiate. Much like stem cells, they still have the potential to become different types of cell, but they have not yet started down the path that will lead to a particular tissue type.
'Cell of origin' for Barrett's esophagus
In the next phase of the study, the team used a method called "lineage tracing" to find out whether the unique primogenitor cells that they discovered can develop into Barrett's esophagus.
They used several mouse models to show how genetic changes or exposure to gall acid reflux can cause the cells to grow and give rise to Barrett's esophagus.
The researchers besides replicated these collection in "organoids" adult from unique basal primogenitor cells sampled from the gastropassage junctions of mice and world. Organoids are multitude of cells that are adult in the laboratory and which have galore of the tissue properties of organs.
In an attendant article, experts comment that the collection set the stage "to investigate whether the transformation epithelial tissue is the sole origin" of Barrett's esophagus, and "what role this tissue has in the progression to opassage cancer."
""Now that we know the cell of origin for Barrett's esophagus, the next step is to develop therapies that target these cells or the signal pathways that are activated by acid reflux."
Prof. Jianwen Que