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Making a trachea from scratch

SCIENCE FILE : Q&A

The process marks another step forward for regenerative medicine.

July 09, 2011|Thomas H. Maugh II

Andemariam Teklesenbet Beyene left a Stockholm hospital Friday, breathing through a manufactured trachea that was built with his own stem cells.

The 36-year-old Eritrean geology student at the University of Iceland in Reykjavik had suffered from an advanced case of tracheal cancer, and tumors were threatening to block his windpipe and choke off his supply of oxygen before the artificial trachea was implanted June 9. Dr. Paolo Macchiarini of Karolinska University Hospital decided there was no time to wait for a donor trachea, so he assembled a team to build one. Since the artificial trachea was made with Beyene's own cells, he hasn't needed anti-rejection drugs that would have suppressed his immune system and made him vulnerable to other infections. He is also cancer-free.

The operation marks another step forward for the field of regenerative medicine and "further validates the fact that these technologies may have a role in treating larger numbers of patients in the future," said Dr. Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest University School of Medicine in Winston-Salem, N.C.

Here's a closer look at Beyene's treatment and what it portends for the future.

What is the trachea?

It's a hollow, Y-shaped tube -- about an inch in diameter and 4 to 6 inches long -- that connects the larynx to the lungs, allowing air to flow into them.

How have they been replacedin the past?

Patients like Beyene relied on tracheas from cadavers, but those are in short supply. Plus, people who receive donor organs must take immune-suppressing drugs for the rest of their lives. The point of developing a synthetic trachea is that the patient's own cells are used to build it, so no immunosuppressive drugs, which have many side effects, are required.

How did the Karolinska team get to this point?

They started several years ago by using a donor trachea as a scaffold to build a new trachea. They stripped away all the cells lining and enclosing the donor trachea, leaving behind only the cartilage-containing skeleton. Using a shoebox-sized bioreactor developed by Harvard Bioscience Inc. of Holliston, Mass., they then seeded some of the patient's own stem cells into the scaffold.

The whole thing was mounted on a rotating drum, similar to a rotisserie for barbecuing chickens. The drum alternately dipped it into a nutrient medium that provided everything needed for the cells to grow and proliferate, and then lifted it out so the cells could get oxygen.

Was that implanted in a person?

Yes. In 2008, Macchiarini and his colleagues reported that they had successfully implanted a semi-synthetic trachea into a Spanish woman named Claudia Castillo, whose trachea had been damaged by tuberculosis. They have since performed the procedure nearly a dozen times on other patients.

What was different this time?

Instead of using a donor trachea for the scaffold, materials scientist Alexander Seifalian of University College London built one in a lab. The base was a glass tube with dimensions obtained from three-dimensional images of Beyene's trachea. Then Seifalian used a medical plastic called polyethylene glycol to build a scaffold around it. The plastic is very porous, allowing the stem cells to grow into it. The scientists put hormones in the nutrient soup to induce the stem cells to change into the cells normally found in the lining and exterior of a trachea. After two days in the bioreactor, the trachea was implanted in Beyene, where the cells continued to grow and proliferate. The whole process took less than a week.

Will they do more?

Macchiarini said the team would perform three more procedures before the end of the year, two on adults from the United States and one on a 9-month-old from North Korea who was born without a trachea.

Is this the first time scientists have made a synthetic body part?

Researchers have used virtually identical techniques to produce synthetic blood vessels, urethras and bladders. The common denominator in all of those is that the synthetic organs are basically hollow tubes or, in the case of the bladder, a hollow sphere. They may have to have the ability to stretch or shrink slightly in response to natural conditions, but they really have no other function.

Producing a more sophisticated organ, such as a heart, will require researchers to make something that actually carries out a function. In the case of a heart, it would have to beat and open and close valves at the appropriate times.

Also, noted Dr. Alan J. Russell, a tissue engineer at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, such solid organs have much thicker tissue and thus need an internal system of blood vessels to supply oxygen and nutrients. That is a far more difficult task.

"That's still years away," said Atala, whose team is trying to make synthetic kidneys.

--

thomas.maugh@latimes.com

Marissa Cevallos of HealthKey contributed to this report.

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