Researchers Dramatically Expanding Study of Regenerated Tissues

Because the world’s second experimental esophagus-replacement surgery—utilizing stem cells—to be performed in Pittsburgh, Pennsylvania, was a success, the surgeon involved will be starting clinical trials of the procedure this September. As reported August 10 by David Templeton of the Pittsburgh Post-Gazette, the surgery took place in 2010, the patient was 56-year-old Mike Wright who had esophageal cancer and the surgeon was Blair Jobe, M.D., with West Penn Allegheny Health Systems. The trial investigators will try to enroll about 40 patients who have Barrett's disease with dysplasia (abnormal cell growth) or early-stage esophageal cancer.

The study will attempt to test whether regrowth of the esophagus lining, as occurred with Mr. Wright, produces better results than the current practice of removing the entire esophagus and then creating a makeshift organ from a portion of the stomach. This invasive procedure, known as an esophagectomy, has been the treatment of choice for esophageal cancers. However, the results have been less than stellar, with a complication rate of 50% and major quality of life issues for the patients. Jobe said.

Jobe has succeeded in replacing the esophageal linings in six patients which represents "proof of principle” for this approach. The scaffolding, developed from pig tissue from which the pig's cells have been removed, is called an "extracellular matrix, " or ECM. As Templeton explained in his report, the ECM contains growth factors and proteins that appear to signal the recipient's adult stem cells to transform themselves into the kind of site-specific cells that are needed at that particular location of the body.

Jobe cuts the cylindrical tube of lining at either end of the damaged area and pulls it out of the throat in a way Templeton describes as being “similar to taking off a tube sock.” Next, Jobe uses pig ECM to form a new esophageal lining. The ECM tube is soaked until it is flaccid and then slipped over a collapsed spring-like stent. He expands the stent until it presses the ECM against the esophageal wall where the lining had been removed. In a process doctors have called “wallpapering, ” the stent holds the ECM in place until it adheres to the wall.

In a matter of days the ECM fully attaches to the esophagus wall to serve as a framework for stem cells to migrate there and heed signals from the ECM or from neighboring esophagus cells to transform into esophageal lining. Soon after the surgery with the stent in place, the patient can consume liquids.

Stephen Badylak, M.D., deputy director of the University of Pittsburgh McGowan Institute for Regenerative Medicine, developed the esophagus-replacement strategy and led the research in removing cells from pig tissue to create a scaffolding that can regenerate damaged tissue. The scaffolding material, now available commercially, has reportedly been used 3 million times worldwide to repair linings, wounds and skin, with efforts presently under way to repair tendons. To date, researchers have reported 10 successful procedures to generate functional new tissue to repair tracheas. Badylak said, "We're batting a thousand, but the numbers are still very low and further studies are definitely warranted."