Down the Hatch Tissue-Engineering Procedure to Save the Esophagus Feeds Effort to Build Human Organs

Article excerpt

Mike Wright's new esophagus continues to work like "a newborn baby's" -- his way of describing the organ he came within weeks of losing in 2010.

The 56-year-old Columbus, Ohio, man -- the world's second to undergo experimental esophagus-replacement surgery in Pittsburgh, his occurring in January 2010 -- remains the biggest cheerleader for the still-experimental surgery soon to be tested in a human clinical trial.

Blair Jobe, a West Penn Allegheny Health Systems surgeon formerly with the University of Pittsburgh Medical Center, is scheduling the clinical trial to begin in September and involving as many as 40 patients who have Barrett's disease with dysplasia (abnormal cell growth) or early-stage esophageal cancer.

The trial will test whether regrowth of the esophagus lining, as occurred with Mr. Wright, produces better results than the current practice of removing the entire esophagus to treat esophageal cancer, then creating a makeshift esophagus with a portion of the stomach. This highly invasive procedure, known as esophagectomy, is the mainstay of therapy for the majority of esophageal cancers and results in a 50-percent complication rate and a long-term quality of life issue, Dr. Jobe said.

Dr. Jobe's success in treating six patients to date without failure represents the latest advance in pioneering tissue- engineering research done at the University of Pittsburgh and UPMC's McGowan Institute for Regenerative Medicine. The current line of research began with the development of two-dimensional tissue replacement, including tubes or tracts and skin, with efforts now under way to replace tendons. The research is progressing to creating whole human organs.

Dr. Jobe said the replacement of esophageal linings in six patients represents "proof of principle for this approach, and we must now validate the results in a clinical trial in order to responsibly introduce this technique into clinical practice." He said there is still a problem of strictures, or a narrowing of the "food tube," in places after the lining restores itself. "But the strictures were stretched open with an outpatient procedure."

It's an issue to be addressed in the clinical trial.

The efforts of Dr. Jobe and the McGowan Institute reflect a worldwide trend in using tissue engineering to treat disease and repair damage. To date, 10 successful procedures to generate functional new tissue to repair tracheas have been reported, while eight patients have received new tissue-engineered bladders. Doctors still must study the patient outcomes, particularly if the procedures were done on a large scale, Dr. Jobe said.

Stephen Badylak, deputy director of the McGowan Institute and noted worldwide for his research in tissue engineering, developed the esophagus-replacement strategy and led research in removing cells from pig tissue to create a scaffolding that can regenerate damaged tissue. The scaffolding material, now available commercially, has been used 3 million times worldwide to repair linings, wounds and skin, with efforts under way to repair tendons.

It's the basis of the esophagus-replacement process. With six successes to date, Dr. Badylak said, "We're batting a thousand, but the numbers are still very low and further studies are definitely warranted." The scaffolding is a key element in research to create new human organs.

Evolution did the hard work of tissue engineering with its method of signalling stem cells to create the needed tissue, Dr. Badylak said. "We have realized the ideal scaffolding during 100 million years of evolution. The hardest part was done by Mother Nature."

The scaffolding is "extracellular matrix," or ECM -- a matrix or tissue framework developed from pig tissue from which all the pig's cells have been removed. The ECM naturally contains growth factors and proteins among other molecules that appear to signal the recipient's adult stem cells, and possibly other cells, to transform themselves into site-specific cells needed at that particular location of the body. …