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Genetic Linkage

Respiratory Replacement Parts -- Thanks to Stem Cells

We humans might not be able to regrow a leg, as can a cockroach or salamander, or regenerate a missing half, like a flatworm, but our organs can replenish themselves – thanks to stem cells. Two new reports about opposite ends of the respiratory system may pave the way for replacement breathing parts.

A 36-year-old grad student from Eritrea was facing certain death from a golf-ball-sized tumor obstructing his trachea and sending tentacles towards his bronchi, the paired tubes that lead into the lungs. He was saved with a “tailored bioartificial nanocomposite” replacement trachea seeded with his own bone marrow stem cells, reported in The Lancet.

Cancer of the trachea is often inoperable and rapidly fatal because even a ventilator can’t push air into the lungs. But the combination of a glass-like tube standing in for the natural cartilage plus the patient’s own stem cells lets biology take over. Extracellular matrix spread over the tube, new capillaries sprouted, and a coat of epithelium knitted itself. The man is now well and lived to see the birth of his child, thanks to the tissue engineers at the Karolinska Institute and the University of Iceland.

Even more exciting is regrowing alveoli, the tiny air sacs that form grape-like clusters at the ends of the bronchioles, inflating and deflating as oxygen enters the bloodstream and carbon dioxide leaves. Taking cues from the ability of survivors of H1N1 influenza to recover, and observing mice grow new alveoli after the flu, researchers from Harvard Medical School and the Genome Institute of Singapore observed human stem cells taken from bronchioles (the passageways between the bronchi and the alveoli) grow and assemble into alveoli.

The lab-grown alveoli reveal that it’s possible to regrow vital lung tissue – not just adapt to what remains after a devastating viral assault. “This study helps clear up the uncertainty. We have found that the lungs do in fact have a robust potential for regeneration, and we’ve identified the specific stem cells responsible,” says senior author Frank McKeon, professor of cell biology at Harvard Medical School. The responsible stem cells are quite rare, and spring into action during infection, sending signals that repair the damaged tissue. The work is published in Cell.

If researchers can safely mimic the jumpstart to respiratory repair that infection sets into motion, then the ability to regenerate or replace parts of the respiratory system can transcend recovery from the flu or conquering cancer. For people with cystic fibrosis or hereditary emphysema (alpha-1 anti-trypsin deficiency), perhaps gene therapy could correct the mutations in the stem cells so that healthy replacement airways and air sacs regrow.

For respiratory ravages due to smoking -- lung cancer and emphysema -- using replacement parts wouldn’t require gene therapy. But choosing patients for what would certainly be a limited medical resource would open a bioethical can of worms akin to the challenge of selecting transplant recipients based on whether they contributed to their illnesses.

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