Growing Human Esophagus Tissue from Human Cells

Tracy Grikscheit of the Saban Research Institute of Children’s Hospital Los Angeles and her colleagues have successfully grown a tissue engineered esophagus on a relatively simple biodegradable scaffold after seeding it with the appropriate stem and progenitor cells.

Progenitor cells have the ability to differentiate into specific cell types and can migrate to a particular target tissue. Their differentiation potential depends on the parent cell type from which they descended and their “niche” or local surroundings. The scaffold upon which these cells were seeded is composed of a simple polymer, but interestingly, several different combinations of cell types were able to generate a replacement organ that worked well when transplanted into laboratory mice.

“We found that multiple combinations of cell populations allowed subsequent formation of engineered tissue. Different progressive cells can find the right “partner” cell in order to grow into specific esophageal cell types; such as epithelium, muscle or nerve cells, and without the need for exogenous growth factors. This means that successful tissue engineering of the esophagus is simpler than we previously thought,” said Grikscheit.

Videos published the paper show a network of muscle cells properly wired with nerves that properly self-organizes whose muscles spontaneously contract.  Such structures are called an esophageal organoid unit (EOU) in culture. Spontaneous contraction is observed within these EOUs.

This study could be the impetus for clinical procedures that can treat children born with portions of their esophagus missing. Since the esophagus carries liquids and food to the stomach from the mouth, it is a vitally important part of the body.

This protocol, could also be applied to patients who have suffered from esophageal cancer and had to have their esophagus removed. Esophageal cancer is one of the fastest growing types of cancer in the United States to date. Alternatively, people who have accidentally swallowed caustic liquids may also benefit from this type of esophageal repair.

This simple scaffold made of a polyglycolic acid/poly-L-lactic acid and coated with the protein collagen is inexpensive and versatile and completely sufficient for the growth of tissue-engineered esophagi from human cells, according to this study. When established in culture, this system can also serve as a model system to study the cell dynamics and physiology of the esophagus.

A deeper understanding of how esophageal cells behave in response to injury and how various donor cells could potentially expand the pool of potential donor cells for engineered tissue.

Even though this technique has only been tested in animals to date, fine-tuning of this technique might very well ready it for clinical trials in the future.

U of Pitt Team Discovers Stem Cells in the Esophagus

Even though several studies have been unsuccessful at identifying a stem population in the esophagus, a study from the University of Pittsburgh has discovered a stem cell pool that services the esophagus. Researchers from the University of Pittsburgh School of Medicine have published an animal report in the journal Cell Reports that might lead to new insights into the development and treatment of esophageal cancer and a precancerous condition known as Barrett’s esophagus.

In the US, more than 18,000 people will be diagnosed with esophageal cancer in 2014 and almost 15,500 people will die from it, according to numbers generated by the American Cancer Society. The precancerous condition known as Barrett’s esophagus is characterized by tissue changes in the lining of the esophagus in which the esophageal lining begins to resemble the tissue architecture of the intestine. Barrett’s esophagus is usually a long-term consequence of gastro-esophageal reflux disease or GERD.

“The esophageal lining must renew regularly as cells slough off into the gastrointestinal tract,” said senior investigator Eric Lagasse, Pharm.D., Ph.D., associate professor of pathology, Pitt School of Medicine, and director of the Cancer Stem Cell Center at the McGowan Institute for Regenerative Medicine. “To do that, cells in the deeper layers of the esophagus divide about twice a week to produce daughter cells that become the specialized cells of the lining. Until now, we haven’t been able to determine whether all the cells in the deeper layers are the same or if there is a subpopulation of stem cells there.”

Lagasse and his team grew small explants of esophageal tissue in culture. These esophageal “organoids” from mice were then used to conduct experiments that were used to identify and track the different cells in the basal layer of the tissue. In these organoids, Lagasse and others found a small population of cells that divide more slowly, are less mature, can differentiate into several different types of esophageal-specific cell types, and have the ability to self-renew. The ability to self-renew is a defining feature of stem cells.

“It was thought that there were no stem cells in the esophagus because all the cells were dividing rather than resting or quiescent, which is more typical of stem cells,” Dr. Lagasse noted. “Our findings reveal that there indeed are esophageal stem cells, and rather than being quiescent, they divide slowly compared to the rest of the deeper layer cells.”

Lagasse and his team would now like to examine human esophageal tissues from patients with Barrett’s esophagus in order to determine if such patients show evidence of esophageal stem cell dysfunction.

“Some scientists have speculated that abnormalities of esophageal stem cells could be the origin of the tissue changes that occur in Barrett’s disease,” Dr. Lagasse said. “Our current and future studies could make it possible to test this long-standing hypothesis.”