Growing 3D vocal cords in a dish

The model could provide insights into treating damaged tissue. Paul Biegler reports. 

Vocal cords are highly sensitive to irritants like cigarette smoke but are hard to study at a molecular and genetic level.

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Researchers have used stem cells to make a 3D model of vocal cords that developed potentially cancer-causing changes after being doused in cigarette smoke extract.

The innovation could lead to genetic and drug therapies for hoarseness, vocal cord polyps and throat cancer, among conditions of the voice box that cost around USD$11 billion a year to treat, according to the authors’ estimates.

The vocal cords are twin slivers of tissue that sit at the top of the windpipe. Much like the reeds of an oboe, the cords vibrate as air passes across them, creating your unique voice. They also stop food titbits going down the wrong hole as they make their way through the gullet.

But the lining of the vocal cords, known as the mucosa, is delicate and takes a decided dislike to irritants including acid reflux, pollution, and the big bogeyman cigarette smoke.

The result is ongoing inflammation and a skin-like thickening of the mucosa called “keratosis” that can herald cancer.

But knowing how these bad guys act at the gene and molecular level is a tall order, given how hard it is to get snippets of vocal cord to study. Unlike, say, a skin sample, you can’t nip a bit of vocal cord from a healthy person without serious issues to their voice.

The researchers, led by Susan Thibeault from the University of Wisconsin Madison in the US, sidestepped that hurdle by growing their very own vocal cords in a dish.

Their primary ingredient was the induced pluripotent stem (iPS) cell, a human-derived cell that can be coaxed to become just about any type of tissue.

Over the course of 32 days Thibeault’s team used a bunch of techniques, including adding something called fibroblast growth factor, to prompt those iPS cells to mirror the layers seen in true vocal cords.

To check the iPS cells were relevantly similar to the real deal they did two things.

First, they grew them alongside cells from actual human vocal cords, labelling the iPS cells with green fluorescence to keep track of them. Then they concocted an extract from the smoke of “research grade” cigarettes and flooded the cells with it for a full week.

In short, the iPS cells behaved very much like their genuine brethren. Neither emerged from the smoking challenge in great shape.

The cigarette extract switched on genes that caused inflammation in the mucosa formed jointly by the stem and vocal cord cells. The result was a dramatic re-configuration of the cells that disrupted the protective mucosal barrier.

It is worth remembering that inflammation is the starting point for a good whack of vocal cord pathology, from nodules through to cancer, so it is potentially a very useful result.

The authors say their 3D model “could provide significant information regarding genetic and molecular regulation of abnormal [vocal cord] mucosa remodeling in response to mucosal inflammation, including identification of targets for possible genetic or pharmacological manipulations.”

The study appears in the journal Nature Communications.

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Paul Biegler is a Eureka-Prize winning journalist, bioethicist and former physician writing on all things health and science.
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