For the first time, researchers have managed to create a human esophagus in the laboratory. This may pave the way for new, regenerative treatments.
This organ is made of different types of tissue, including muscle, connective tissue, and mucous membrane.
Scientists at the Cincinnati Children’s Center for Stem Cell and Organoid Medicine (CuSTOM) in Ohio have artificially grown these tissues in the laboratory using pluripotent stem cells, or stem cells that can take any form and create any tissue in the body.
The team — which was led by Jim Wells, Ph.D., the chief scientific officer at CuSTOM — grew fully formed human esophagi in the laboratory and detailed its findings in a paper published in the journal Cell Stem Cell.
To their knowledge, this is the first time that such a feat has been achieved using only pluripotent stem cells.
They may also help treat more rare congenital diseases, such as esophageal atresia (a condition in which the upper esophagus does not connect with the lower esophagus) and esophageal achalasia (wherein the esophagus does not contract and so cannot pass food).
As Wells and team explain in their paper, having a fully functional model of the human esophagus — in the form of a laboratory-grown organoid — contributes to a better understanding of these diseases.
The findings may also lead to better treatments using regenerative medicine.
As they were trying to form the organoids, Wells and team focused on a protein called Sox2 and the gene that encodes it. Previous research had shown that disruption in this protein leads to a range of esophageal conditions.
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.
They also wanted to study the effects of Sox2 deprivation in these key developmental stages. The experiment revealed that the loss of Sox2 resulted in a form of esophageal atresia in the mice.
Finally, they were able to create esophagus organoids that were 300–800 micrometers long at 2 months. The scientists then tested the composition of the laboratory-grown tissues and compared it with that of human esophageal tissue obtained from biopsies.
Wells and team report that the two types of tissue had a very similar composition. Wells comments on the clinical significance of the organoids, saying:
“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.”
“Disorders of the esophagus and trachea are prevalent enough in people that organoid models of human esophagus could be greatly beneficial.”
Jim Wells, Ph.D.