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From stem cells to hair cells

One of the main barriers to developing treatments for hearing loss is how hard it is to study the human inner ear. Tracey Pollard, from our Biomedical Research team, tells us about recent research we supported that aimed to turn stem cells into inner ear hair cells.

To really be able to successfully develop treatments for hearing loss, to be able to re-grow the sound-sensing cells in the inner ear to restore hearing, we need to know more about them. To do this, we need to be able to study human hair cells and the human inner ear directly. This is much easier said than done!

The inner ear is hidden in the skull behind the hardest bone in the human body, making it nearly impossible to access. But even if we could get to it, we couldn’t remove it, or any of the cells within it, without destroying its delicate architecture and damaging someone’s hearing.

It’s possible to study hair cells in animals such as the mouse, and many researchers have done just that – but while we can find out a lot from studying them, it’s not the same as studying our own hair cells. Studying hearing in animals gives us invaluable information, but we need to study human cells directly to be able to develop effective treatments.

How we can do this

One approach is to use stem cells. Stem cells can turn into any other type of cell and divide to make more stem cells – once they turn into, for example, a skin cell or a hair cell, they lose most, if not all, of these abilities. This is why hearing loss caused by loss of hair cells is permanent – our hair cells don’t re-grow.

Researchers have been using stem cells to study how various cell types develop, to better understand what goes wrong in disease and, if possible, how to put it right. This includes researchers studying hearing loss – they’ve been trying to turn stem cells into sound-sensing hair cells. Development of all cells into their final form is a complicated process, so figuring out how to do this has involved a lot of trial and error!

A group of researchers at Indiana University in the US, led by Professor Eri Hashino and Dr Karl Koehler, have been working on this problem, and they’ve managed to find a way to turn stem cells into hair cells in the lab. They started with mouse stem cells, but have more recently moved on to working with human stem cells.

Growing hair cells in the lab

Using mouse stem cells, the researchers found a way to make them develop into structures called ‘inner ear organoids’ (organoid literally means ‘little organ’). They did this by growing the stem cells in a three-dimensional system (as opposed to how cells are usually grown in the lab, in flat layers in a tissue culture dish). This helped the cells to form structures similar to the actual mouse inner ear. They also exposed the cells to a number of different chemicals that were known to be involved in the correct formation of hair cells.

The team changed how much of each chemical they added, when they added it, and how long for, until they were able to consistently grow inner ear organoids in the lab. These organoids contained cells that looked and behaved like normal hair cells – that is, they could produce electrical signals and they formed appropriate connections to nerve cells in the organoid. The main function of a hair cell is to turn sound information into electrical signals that the brain can understand, and to pass them onto the brain via nerve cells, so it’s important that these cells could do these things.

Producing human hair cells

Professor Hashino and her team then turned their attention to human stem cells. They couldn’t use the same method that they’d used with the mouse cells; it didn’t work. Human stem cells differ from mouse stem cells in a number of ways, and in general, they’re harder to work with. In the end, they used many of the same chemicals to turn human stem cells into hair cells (a human inner ear organoid is pictured) – the main difference was that they had to add them for longer and at different times. Human stem cells take longer to fully develop into hair cells, which perhaps isn’t such a surprise when you consider that mice live for up to 3 years, while humans can live to be over 100! Just like the mouse cells, however, the human hair cells could generate electrical signals and form connections to nerve cells.

What does this mean for treatments?

Although the ability to grow human hair cells in the lab is a huge advance for the hearing research field, it’s an early step towards developing treatments to restore hearing in people. Having these cells available makes it easier to study the inner ear in people, and what happens when human hair cells die, and they’re important for testing potential methods of re-growing hair cells. Unlike birds, which can re-grow their hair cells, we can’t – but if we could find ways to switch on the processes that allow birds to re-grow their hair cells in human hair cells, we’d be able to develop treatments to restore hearing in people.

Another use of these cells could be to identify drugs that damage hair cells and cause hearing loss (like certain antibiotics and anti-cancer drugs do), or to identify drugs that could protect hair cells from damage when people have to take these life-saving medicines.

It’s important to note that the hair cells developed in this work resemble hair cells from the vestibular system in the inner ear, which controls our balance. Vestibular system hair cells are similar to hair cells from the cochlea (the hearing organ), but they’re not the same. We can learn a lot by studying them, but we’ll need to wait until researchers can produce cochlear hair cells before the real work to develop treatments for hearing loss can begin. This is a great start, though – and we hope we won’t have too long to wait!

Further information

The human stem cell work was published earlier this year in the journal Nature Biotechnology – you can read the abstract on the PubMed website.

The mouse stem cell work was published in 2013 in the journal Nature – you can read the full text of the article on PubMed Central.

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