Tissue Engineering to Regrow the Esophageal Lining

The use of decellularized animal tissue as a basis for reconstructive therapies is spreading: the tissue can be stripped of cells leaving only the extracellular matrix to act a growth-inducing scaffold for a patient's own cells - and with no immune rejection issues, even though it came from a different species. With these tools it is possible to rebuild a wider range of tissues than in the past, and produce a better end result. Much of the public attention on tissue engineering focuses on the end goal of complex organs built from scratch, new hearts, kidneys, and livers, but this remains a decade or more in the future. Meanwhile a great deal of presently achievable work is already taking place, the reconstruction and replacement of less complex structures in the body such as the trachea.

A recent article goes into some detail as to how decellularized pig tissues are used to greatly improve one particular form of reconstructive therapy:

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. ... 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.


Dr. Jobe's success in treating six patients to date without failure represents the latest advance in pioneering tissue-engineering research ... 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."


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. ... For the right candidate for the surgery, Dr. Jobe cuts the cylindrical tube of lining at either end of the damaged area [of the esophagus], as if he were removing a damaged piece of pipe, before pulling it out of the throat in a way similar to taking off a tube sock. If nothing else were done, resultant scarring would prevent swallowing and clog the throat. The ECM process regenerates healthy tissue without scarring.

Next Dr. Jobe uses pig ECM that Dr. Badylak developed and now produced commercially to form a new esophageal lining. The ECM tube is soaked until it is flaccid and then slipped over a collapsed spring-like stent. Once in place, the stent is expanded until it presses the ECM against the esophageal wall where the lining had been removed. In a process known as 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 or other 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. Full replacement of the lining occurs within several weeks. In time, the pig ECM is replaced naturally with human tissue. Mr. Wright said he can eat and drink anything he wants without any difficulty in swallowing.

As the article points out, this is a big improvement over the previous form of surgical reconstruction of the esophagus, which tends to have a high rate of complications and quality of life issues. This sort of incremental improvement will continue throughout the years between now and the development of means to build entire organs like hearts and lungs from nothing more than a patient's own cells. This isn't just a matter of waiting for a distant goal, but a matter of constant, ongoing progress in the quality and effectiveness of medicine.


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