Scientists grow human esophagus using stem cells

WASHINGTON, Sept. 20  - American scientists grew human esophageal organoids entirely using pluripotent stem cells (PSCs) for the first time, potentially leading to new personalized diagnostic methods and regenerative tissue therapies to treat or cure gastrointestinal disorders.

The study published on Thursday in the journal Cell Stem Cell reported a new method that used human PSCs to produce general esophageal tissues on precisely timed, step-by-step manipulations of genetic and biochemical signals that pattern and form embryonic endoderm and foregut tissues.

"In addition to being a new model to study birth defects like esophageal atresia, the organoids can be used to study diseases like eosinophilic esophagitis and Barrett's metaplasia, or to bioengineer genetically matched esophageal tissue for individual patients," said Jim Wells, chief scientific officer at Cincinnati Children's Center for Stem Cell and Organoid Medicine (CuSTOM) and study lead investigator.

The esophagus is a muscular tube that actively passes food from the mouth to the stomach.

The fully formed human esophageal organoids grew to a length of about 300 to 800 micrometers in about two months. Those tests showed the bioengineered and biopsies tissues were strikingly similar in composition, according to the study.

The scientists focused in part on the gene Sox2 and its associated protein. They used mice, frogs and human tissue cultures to identify other genes and molecular pathways regulated by Sox2 during esophagus formation.

They found that during critical stages of embryonic development, the Sox2 gene blocks the programming and action of genetic pathways that direct cells to become respiratory instead of esophageal.

In addition, Sox2 protein can inhibit the signaling of a molecule called Wnt and thus promote the formation and survival of esophageal tissues, according to the study.

In another test to help confirm the importance of Sox2 expression on esophageal formation, researchers studied the complete loss of Sox2 during the development process in mice.

The absence of Sox2 resulted in esophageal agenesis, a condition in which the esophagus terminates in a pouch and does not connect to the stomach.

The research team is continuing its studies into the bioengineering process for esophageal organoids and identifying future projects to advance the technology's eventual therapeutic potential, according to Wells.