Rob Coppes grows salivary glands
Using stem cells to combat dry mouth
Sometimes, you need to have a little patience.
Professor of radiology Rob Coppes remembers exactly when he came up with his revolutionary method to grow salivary glands. It was twenty years ago; he was attending a conference in Oxford where a scientist was talking about his research, in which he used cultured nerve cells to repair the spinal cord in people with localised paralysis.
‘I thought to myself: maybe we could do the same with salivary glands.’
A few years later, someone published an article in Nature about a so-called multipotent stem cell harvested from bone marrow that had the ability to grow into different kinds of tissue, and Coppes realised he’d found a way to start his experiments. Unfortunately, he didn’t succeed, mainly because it turned out the article was fraudulent, but it did give Coppes and his colleagues some new ideas. ‘You might be looking in the wrong direction sometimes, but if you just pay attention, you’ll eventually find your way.’
Eating and talking
Coppes was trying to find treatment for patients suffering head and neck cancers. 40 percent of them suffer from dry mouth after radiation therapy because their salivary glands produce very little saliva, if at all. ‘Without saliva, daily tasks like eating and talking become that much more difficult. On top of that, saliva also protects your teeth from acids, as well as your mouth from bacteria and viral infections.’
Without saliva, daily tasks become that much more difficult
Coppes regularly talks to patients, listening to their stories about how the lack of saliva has impacted their lives. One patient had to quit his teaching job, because he was unable to talk for that long. ‘That’s great motivation to do my very best!’
Initially, Coppes was looking for a drug, something that would enable broken cells to repair themselves. But two decades after that conference in Oxford, he’s invented a way for the patients’ stem cells to create new salivary glands themselves.
A single brick
Figuring this out wasn’t easy. You can take stem cells from bone marrow and inject them into the bloodstream. ‘You just draw some blood and separate the cells’, Coppes says. But when it comes to other tissue, such as the salivary glands, the cells need to be extracted from the tissue itself. ‘I like to compare it to a house’, says Coppes. ‘The cells are all stuck together with cement, and all you need is a single brick from the wall of the house. That one stem cell is important.’
At first, Coppes didn’t know where in the salivary glands the stem cells were located. Finding them was one of his first big victories. After that, he had to figure out if the cells could grow into new salivary glands. That, too, was a complicated process. Eventually, Coppes and his colleagues managed to get the cells to grow, but that process couldn’t even remotely be applied to human subjects. ‘I had to use the cells from three separate mice just to successfully treat a single mouse.’
Those cells are all stuck together with cement
But then, Hans Clevers, pioneer in the field of organoids – miniature versions of organs that can be grown outside the body – published his work. His culture methods provided the last step in Coppes’ research. He added the wnt signalling protein, a molecular signal that activates stem cells, using it to improve the cells’ development. ‘They finally grew into a full-blown salivary gland.’
It was a giant leap forward. ‘I still remember the student who was working on it. They came up to me and said: “Rob, you have to come take a look at the microscope”’, Coppes recounts, laughing. ‘I was only the second person in the world to see them!’
This means he’s now found a way to actually inject the salivary glands that he used to only be able to imagine into real, human patients. ‘We first operate on the patient to remove the tumour’, says Coppes. ‘During the surgery, we then isolate a bit of the salivary gland that we use to extract the stem cells from.’ Once the patient has finished radiation therapy and their mouth has healed, they receive the stem cells that Coppes has grown in his laboratory.
Last December, the very first patient received their injection.
You don’t learn much and things often go wrong
The operation room was filled to the brim: not only was the patient’s wife in attendance, but so was the radiologist, and there was even a camera crew. It was a special day for everyone, including Coppes. ‘It was the very first time, so I really wanted everything to go well’, he says. ‘And to be honest, the procedure looked pretty painful.’
Fortunately, any discomfort the patient may have felt was gone the next day. In fact, three months later, he emailed Coppes to tell him that he no longer needed a glass of water when he woke up; he could feel some saliva in his mouth! Whether this is a direct result of the injection will have to be revealed through scans. ‘But it’s a better result than if nothing had happened.’
Least favourite part
Eighteen people will be treated with Coppes’ experimental salivary glands. Four of them have already been injected. Once all eighteen of them have been treated, it will mean Coppes can take the next step in his clinical trial – before the treatment can be approved by the Central Committee on Research Involving Human Subjects, he has to prove that it works and that it’s safe. ‘It involves endless clinical testing. It’s my least favourite part, because you don’t learn much and things often go wrong.’
Nevertheless, Coppes has hope. He saw how his lab animals regained 80 percent of their original saliva production capabilities. If he reaches even 25 percent in human subjects, he thinks it would help them a lot with the daily issues of eating and talking.
In the meantime, he keeps looking ahead. He wants to figure out if his method could also work for people with thyroid cancer. Those people have their entire gland removed during surgery, so it would be great if he could give them a new thyroid.
First, he needs to finish his project on salivary glands. ‘My goal is to finish it before I retire in five years, and to have the follow-up study already underway.’