Scientists Grow Human Esophagus in Lab


Source: Cincinnati Children’s Hospital Medical Center

Summary: Scientists working to bioengineer the entire human gastrointestinal system in a laboratory now report using pluripotent stem cells to grow human esophageal organoids.


The esophagus is a muscular tube that actively passes food from the mouth to the stomach. The organ can be affected by congenital diseases, such as esophageal atresia, a narrowing or malformation of the esophagus caused by genetic mutations. Additionally, there are several diseases that can afflict people later in life. Some include esophageal cancer, gastroesophageal reflux disease (GERD), or a rare ailment called achalasia, a disease affecting the muscles of the lower esophagus that prevents contraction of the organ and the passage of food. All of the conditions need better treatments, researchers note. This requires a more precise understanding of the genetic and biochemical mechanisms behind their cause. Researchers at researchers at the Cincinnati Children’s Center for Stem Cell and Organoid Medicine are working to bioengineer the entire human gastrointestinal system in a laboratory now report using pluripotent stem cells (PSCs) to grow human esophageal organoids. The study findings were published in the journal Cell Stem Cell.

Esophagus

This confocal microscopic image shows a two-month-old human esophageal organoid bioengineered by scientists from pluripotent stem cells. About 700 micrometers (0.027 inches) in size, the organoid is stained to visualize key structural proteins expressed in mature esophagus, such as involucrin (green) and cornulin (blue). Credit: Cincinnati Children’s Hospital Medical Center

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. They focused in part on the gene Sox2 and its associated protein which are already known to trigger esophageal conditions when their function is disrupted. The scientists report that during critical stages of embryonic development, the Sox2 gene blocks the programming and action of genetic pathways that direct cells to become respiratory instead of esophageal. In particular, the Sox2 protein inhibits the signaling of a molecule called Wnt and promotes the formation and survival of esophageal tissues. After successfully generating fully formed human esophageal organoids which grew to a length of about 300-800 micrometers in about two months, the bioengineered tissues were compared biochemically to esophageal tissues from patient biopsies. Those tests showed the bioengineered and biopsies tissues were strikingly similar in composition.

Chief scientific officer Jim Wells said, “Disorders of the esophagus and trachea are prevalent enough in people that organoid models of human esophagus could be greatly beneficial.”


More Information: Stephen L. Trisno et al, “Esophageal Organoids from Human Pluripotent Stem Cells Delineate Sox2 Functions during Esophageal Specification”, Cell Stem Cell (2018).  DOI: 10.1016/j.stem.2018.08.008


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