In a first, scientists have successfully grown oesophageal organoids — miniature, functional versions of the human food pipe — using stem cells, paving the way for new ways to study and test drugs against gut disorders.
The research, published in the journal Cell Stem Cell, shows how human oesophageal tissue was grown entirely from pluripotent stem cells (PSCs), which can form any tissue type in the body. The work by researchers at the Cincinnati Children’s Center for Stem Cell and Organoid Medicine (CuSTOM) in the US may lead to personalised diagnostic methods and focused in part on developing regenerative tissue therapies to treat or cure GI disorders.
“Disorders of the esophagus and trachea are prevalent enough in people that organoid models of human esophagus could be greatly beneficial,” said Jim Wells, a chief scientific officer at CuSTOM. “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,” Wells said.
The oesophagus is a muscular tube that actively passes food from the mouth to the stomach. The organ can be affected by congenital diseases, such as oesophageal atresia — a narrowing or malformation of the oesophagus caused by genetic mutations. There are several diseases that can afflict people later in life. Some include oesophageal cancer, gastroesophageal reflux disease (GERD), or a rare ailment called achalasia — a disease affecting the muscles of the lower oesophagus that prevents contraction of the organ and the passage of food.
All of the conditions need better treatments, researchers said. This requires a more precise understanding of the genetic and biochemical mechanisms behind their cause — a need filled by the ability to generate and study robust, functional, genetically matched models of human oesophageal tissue that can be grown from a person’s own cells.
After successfully generating fully formed human esophageal organoids — which grew to a length of about 300-800 micrometres in about two months — the bioengineered tissues were compared biochemically to oesophageal tissues from patient biopsies. Those tests showed the bioengineered and biopsies tissues were strikingly similar in composition, researchers said.