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Scientists working on the bioengineering of the entire human gastrointestinal system in a laboratory are now reporting the use of pluripotent stem cells for the growth of organoids in the human esophagus.
Posted in the journal Cell strain cell The study is the latest advance by researchers at the Cincinnati Children's Center for Stem Cell and Organoid Medicine (CuSTOM). The center is developing new ways to study congenital anomalies and diseases that affect millions of people suffering from gastrointestinal disorders, such as gastric reflux, cancer and others. This work leads to new methods of personalized diagnosis and focuses in part on the development of regenerative tissue therapies to treat or treat gastrointestinal disorders.
According to the authors, the new published study is the first time that scientists have been able to develop human esophageal tissues from pluripotent stem cells (PSCs), which can form any type of tissue in the body.
Cincinnati Children's Scientists and their multi-institutional collaborators have already used PSCs to bioengineer the human gut, stomach, colon and liver.
"The disorders of the esophagus and trachea are quite prevalent in people as the organoid models of the human esophagus could be very beneficial," said Jim Wells, chief scientist of CuSTOM and senior research scientist. # 39; study. "In addition to being a new model for studying congenital anomalies such as oesophageal atresia, organelles can be used to study diseases such as eosinophilic esophagitis and Barrett's metaplasia.
The food chain
The esophagus is a muscular tube that puts food from the mouth to the stomach. The organ can be affected by congenital diseases, such as atresia of the esophagus, narrowing or malformation of the esophagus caused by genetic mutations.
In addition, many diseases can affect people later in life. Some include esophageal cancer, gastroesophageal reflux disease (GERD) or a rare condition called achalasia – a condition that affects the muscles of the lower esophagus and prevents contraction of the organ and the passage of food.
All conditions require better treatments, the researchers note. This requires a more precise understanding of the genetic and biochemical mechanisms at the origin of their cause – a need bridged by the ability to generate and study robust, functional, and genetically compatible models of human esophageal tissue that can be grown from own cells of a person.
Tracing the path of nature
Scientists have based their new method of using human CSPs on general oesophageal organoids during minute step-by-step manipulation of genetic and biochemical cues that form and form endodermal and intestinal embryonic tissues.
They focused in part on the Sox2 gene and its associated protein, which are already 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.
Scientists report that 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. In particular, the Sox2 protein inhibits the signaling of a molecule called Wnt and promotes the formation and survival of oesophageal tissues.
In another test aimed at confirming the importance of Sox2 expression on esophagus formation, the researchers investigated the complete loss of Sox2 during the developmental process in mice. The absence of Sox2 has resulted in oesophageal agenesis – a condition in which the esophagus ends in a pocket and does not connect to the stomach.
After successfully producing fully formed human esophageal organoids, which reached a length of about 300 to 800 micrometers in about two months, the transgenic tissues were compared biochemically to the tissues of the liver. esophagus from biopsies of patients. According to the authors, these tests showed that the transgenic tissues and biopsies had a surprisingly similar composition.
The research team is continuing its studies on the bioengineering process of oesophageal organelles and identifying future projects to advance the therapeutic potential of the technology, according to Wells.
This includes the use of organelles to examine the progression of specific diseases and congenital anomalies affecting the esophagus.
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