First human oesophagus created in lab using stem cells

Henrietta Strickland
September 24, 2018

Scientists in the U.S., working to recreate the entire human gastrointestinal tract by biomechanical methods in the laboratory, have announced that they have succeeded in developing human esophagus tissue through the cultivation of pluripotent stem cells.

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 researchers, headed by Jim Welles of the Cincinnati Children's Hospital's Medical Center, made the relevant publication in the journal Cell Biology, Cell Stem Cell.

Esophageal atresi, a narrowing or malformation of the esophagus caused by genetic mutations, is among congenital diseases of the organ.

"Disorders of the esophagus and trachea are prevalent enough in people that organoid models of human esophagus could be greatly beneficial", Wells says.

Cincinnati Children's scientists and their multi-institutional collaborators already have used pluripotent stem cells to bioengineer the human intestine, stomach, colon and liver.

The esophagus is the muscular tube that moves the food and liquids we ingest from our throats all the way to our stomachs. Esophageal cancer is one example, but gastroesophageal reflux or achalasia can also reduce function and put a person's life at risk.

All of the conditions need better treatments, researchers note.

The team points out that all these conditions require better treatments, and to reach them, it is important that both the genetic and biochemical mechanisms at play in the esophagus are understood. This is why using these organoids could be a game changer.

As they were trying to form the organoids, Wells and team focused on a protein called Sox2 and the gene that encodes it. So, they compared their version which was grown in a lab to esophageal tissue biopsied from patients. - The scientists used mice, frogs and human tissue cultures to identify other genes and molecular pathways regulated by Sox2 during esophagus formation.

They found that during embryonic development the gene blocks of the genetic team, due to which the cells could develop into part of the respiratory system.

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.

Conversely, the absence of Sox2 during the development process in mice can result in oesophageal agenesis - a condition in which the oesophagus terminates in a pouch and does not connect to the stomach.

They plan to adapt their process to the progression of specific diseases and congenital defects affecting the esophagus.

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