Human embryonic stem cells restore hearing in deaf gerbils

Ever since human embryonic stem cells (hESCs) were first cultivated by Dr. James Thompson at the University of Wisconsin, Madison in 1998, they have been at the centre of one of the most promising, and at times controversial, areas of modern medicine.  Recently hESCs have begun to live up to their early promise, as I discussed in a recent post on the launch of a clinical trial of hESC-dericed retinal cells in restoring vision in Stargart’s Macular Dystrophy.

Now a study from the University of Sheffield – published this week in the prestigious scientific journal Nature (1) – indicates that hESCs may be able to restore hearing as well as vision, by showing that auditory nerve cells derived from hESCs could restore hearing in deaf gerbils.  While this is not the first time that auditory nerve cells have been created from hESCs, it is the first time that it has been demonstrated that they can restore the connection between the sensory hair cells that convert sound vibration into electrical signals and the brain, and demonstrated improvements to hearing. A commentary in Nature News discusses the work led by Dr. Marcelo Rivolta:

Rivolta has spent the past decade developing ways to differentiate human embryonic stem cells into the two cell types that are essential for hearing: auditory neurons, and the inner-ear hair cells that translate sound into electrical signals.

He treated human embryonic stem cells with two types of fibroblast growth factor (FGF) — FGF3 and FGF10 — to produce two, visually distinct, groups of primordial sensory cell. Those that had characteristics similar to hair cells were dubbed otic epithelial progenitors (OEPs), and those that looked more like neurons were dubbed otic neural progenitors (ONPs).

His team then transplanted ONPs into the ears of gerbils that had been treated with ouabain, a chemical that damages auditory nerves, but not hair cells. Ten weeks after the procedure, some of the transplanted cells had grown projections that formed connections to the brain stem. Subsequent testing showed that many of the animals could hear much fainter sounds after transplantation, with an overall improvement in hearing of 46%”

Gerbils were used in this study rather than the more usual mice because they hear sounds in the same frequency range as humans, whereas the hearing of mice functions best at higher frequencies.

Human ESC derived optic nerve cells (yellow) repopulate the gerbil cochlea. Credit: Marcelo Rivolta, University of Sheffield.

You can read more about the work on the University of Sheffield website, where Dr. Rivolta has published a discussion of his groups work.

It will be some time before this approach can be evaluated in human trials, as further animal studies will need to be undertaken to both improve the efficiency of the procedure so that greater improvement to hearing results, and to demonstrate efficacy and safety over longer periods of time (this study lasted only 10 weeks). It is also clear that this technique will need to be adapted to address the different causes of deafness, for example deafness may be due to damage to sensory cells, or to the auditory nerve that passes the message to the brain, or to both.

Insertion of the stem cells into the cochlea will require surgery, and the techniques required for this in human patients will need to be developed over the coming years, but over 200,000 people worldwide have now been fitted with cochlear implants, so the technical challenges involved are not insurmountable.  Cochlear implants are used to restore hearing to many deaf people, but require a functioning auditory nerve, so hESC derived auditory neurons could be used alongside cochlear implants to restore hearing to many people who cannot currently benefit from these implants. Indeed the potential of combining cochlear implants with stem cell therapy was a major motivation for concentrating on the auditory nerve in this initial study, as Dr. Rivolta noted in a statement to ScienceNow:

Obviously the ultimate aim is to replace both cell types, but we already have cochlear implants to replace hair cells, so we decided the first priority was to start by targeting the neurons.”

There’s no doubt that this is an exciting piece of research in its own right, and of course another example of how the field of stem cell research is maturing, but what’s also been very refreshing is how Dr. Rivolta and his colleagues at the University of Sheffield have been will to discuss their use of animals in research with the press, with reports appearing in numerous outlets including the BBC, Guardian, ABC news, Times of India, Fox and  Montreal Gazette. It is further evidence – if any is still needed – that when scientists are open about their use of animals in biomedical research they will find that there are many journalists and news editors do understand the value of such work, but it is equally certain that in order to report animal research accurately journalists need scientists and scientific institutes to engage with them and provide the detailed information to inform their articles. The message to the scientific community could not be any clearer; if you wish the public to understand your work, take the time to explain it to them.

Paul Browne

1)      Chen W, Jongkamonwiwat N, Abbas L, Eshtan SJ, Johnson SL, Kuhn S, Milo M, Thurlow JK, Andrews PW, Marcotti W, Moore HD, Rivolta MN. “Restoration of auditory evoked responses by human ES-cell-derived otic progenitors.” Nature. 2012 Sep 12. doi: 10.1038/nature11415. [Epub ahead of print] Pubmed: 22972191

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