Scientists grow human esophagus using stem cells

Desiree Burns
September 24, 2018

Scientists in the United States, 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.

In a first, U.S. scientists have used stem cells to grow human oesophagus - known as the food pipe - in the laboratory, an advance that will enable personalised disease diagnosis, regenerative therapies. The feat was led by a team from the Cincinnati Children's Center for Stem Cell and Organoid Medicine (CuSTOM).

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 linking the mouth to the stomach. It will serve as an experienced model for the study of congenital and acquired diseases, such as esophageal atresia, eosinophilic esophagitis, esophageal cancer and many others.

"Disorders of the oesophagus and trachea are prevalent enough in people that organoid models of human oesophagus could be greatly beneficial", said lead investigator Jim Wells, from the hospital. For all these ailments, better treatments are sought from today.

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.

The fully formed human esophageal organoids grew to a length of about 300 to 800 micrometers in about two months.

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The scientists based their new method for using human PSCs to general esophageal organoids on precisely timed, step-by-step manipulations of genetic and biochemical signals that pattern and form embryonic endoderm and foregut tissues.

The scientists cultured human tissue cells, as well as cells from the tissues of mice and frogs, to examine more closely the role of Sox2 in the embryonic development of the esophagus.

The team revealed that Sox2 drives the formation of esophageal cells by inhibiting another genetic pathway that would "tell" stem cells to form into respiratory cells instead.

When the researchers compared the lab-grown esophageal tissue to tissues biopsied from patients, they found the two were "strikingly similar in composition", according to a press release.

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. When "off" Sox2 esophagus of rodents ended with a little pouch and was not connected with the stomach.

The team will continue to investigate these organoids and focus on ways to advance the technology.

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