First human esophagus created in the laboratory with the help of stem cells

A human embryonic stem cell line derived from Stanford University is illustrated in this photo distributed to Reuters by the California Institute for Regenerative Medicine on March 9, 2009. (Reuters)

As a first step, US scientists have used stem cells in the laboratory to cultivate the human esophagus, known as the "alimentary tube", which will allow a personalized diagnosis of diseases and regenerative therapies. A team from Ohio's Cincinnati Children's Hospital has been successful in producing fully formed human oesophageal organoids – a tiny version of a three-dimensional in vitro organ – using pluripotent stem cells (PSCs).

CSPs are master cells that can potentially produce any cell or tissue that the body needs to repair itself. The esophageal organelles reached about 300 to 800 micrometers in about two months.

"The disorders of the esophagus and trachea are quite prevalent in people as the organoid patterns of the human esophagus could be very beneficial," said principal investigator Jim Wells of the 39; hospital.

"In addition to being a new model for studying congenital anomalies such as esophageal atresia, organelles can be used to study diseases such as oesosinophilic esophagitis and Barrett's metaplasia.

In the study, published in the journal Cell Stem Cell, the team focused on the Sox2 gene and its associated protein – known to trigger oesophageal conditions when their function is disrupted.

Scientists used mouse cultures, frogs and human tissue to identify other genes and molecular pathways regulated by Sox2 during esophagus formation.

During critical stages of embryonic development, the Sox2 gene blocks the programming and action of the genetic pathways that direct cells to become respiratory instead of the esophagus.

The Sox2 protein inhibits the signaling of a molecule called Wnt and promotes the formation and survival of oesophageal tissues.

Conversely, the absence of Sox2 during the developmental process in mice can result in oesophageal agenesis – a condition in which the esophagus ends in a pocket and does not connect to the stomach.

These tests showed that the composition of transgenic tissues and biopsies was surprisingly similar, the team said.

Scientists at Cincinnati Children have used CSPs to bioengineer the human gut, stomach, colon and liver.