Researchers have grown a mini esophagus from stem cells.
Scientists at the Cincinnati Children’s Center for Stem Cell and Organoid Medicine (CuSTOM) are developing new methods for studying birth defects and diseases that affect the gastrointestinal (GI) tract. Previous successes have included engineering of human intestines, stomach, colon and liver tissue from pluripotent stem cells. The most recent advance involves the growth of esophageal organoids (mini esophagi) entirely from stem cells.
The organoids reached lengths of 300 to 800 micrometers within two months. By comparing the grown tissue to human esophageal tissue from patient biopsies, it was determined that the engineered organoids were similar to human esophageal tissue.
Growth of the mini esophagi was achieved using the Sox2 gene and its associated protein, as well as other genes and pathways that Sox2 plays a role in during esophagus formation—these were identified by studying frogs, mice and human tissue. Sox2was found to block genetic pathways that cause cells to become respiratory rather than esophageal. Deletion of the gene in mice led to esophageal agenesis, a condition in which the esophagus ends in a pouch rather than connecting with the stomach.
The hope of the group is to eventually bioengineer the entire human gastrointestinal system and then develop regenerative—and potentially curative—treatments for GI diseases. The researchers are first investigating how the organoids can be further advanced so that they can be used to study the progression of specific diseases and congenital defects that affect the esophagus.
"In addition to being a new model to study birth defects like esophageal atresia (bi-segmented esophagus), 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, Ph.D., Chief Scientific Officer at CuSTOM and study lead investigator.