EARLIER this year came news of a second successful voice box transplant. But the recipient, Brenda Jensen, was able to have a new larynx only because she was already taking immunosuppressant drugs to stop her transplanted kidney and pancreas being rejected.
Now Paolo Macchiarini of the Karolinska Institute in Stockholm, Sweden, and colleagues in Italy are developing a technique to treat the donor larynx so that the recipient’s body accepts it as its own – and they have just announced their first successful partial transplant.
The donor larynx is stripped of its cells and reseeded with stem cells from the recipient
For a transplant to work, recipients usually have to take immunosuppressants for life to avoid rejecting the foreign tissue. The trouble is that these drugs can reduce life expectancy by 10 years, making it difficult to justify a larynx transplant in an otherwise healthy person when it’s not critical for their survival, says Peter Belafsky at the University of California, Davis, who operated on Jensen.
Macchiarini’s technique solves the rejection problem by stripping the donor tissue of cells and DNA before reseeding it with stem cells taken from the recipient’s bone marrow. His team previously pioneered this bioengineering technique for human windpipe transplants.
“But the larynx is more complex than a windpipe,” says Macchiarini. To find out if the technique could be adapted, his team gained consent to remove the larynxes from five cadavers and treated them with enzymes and detergents to remove donor cells. Tests showed that just 0.001 per cent of donor DNA remained – quantities small enough to suggest they could be transplanted without rejection.
The larynx contains two types of cartilage – elastic and hyaline – each with distinct properties. The stripped larynxes showed similar mechanical properties to those of a normal larynx, suggesting they could perform with the same degree of versatility after transplant.
Finally, the researchers showed that blood vessels would regrow in the treated larynxes, making it easier for them to integrate with the recipient’s body after transplant (Biomaterials, DOI: 10.1016/j.biomaterials.2011.02.055).
In work still to be published, the team describe how they transplanted the cricoid into a patient. This lower section of the larynx is simpler than the upper part and mainly provides structural stability.
They stripped the donor’s cells from the cricoid and seeded its outer surface with the recipient’s adult stem cells to grow chondrocytes, the cells found in cartilage. “Stem cells were also used to flush the internal surface and seed islets of respiratory cells,” says Macchiarini, before the cricoid was transplanted.
Although the researchers are still some way from a full bioengineered larynx transplant, Belafsky is impressed. “It’s light years ahead of anything that anyone else is doing,” he says.
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