Could we regrow hair cells?
Attempts to regrow lost hair cells in the cochlea to restore hearing are focussed on two main areas – developing stem cell therapies that can be implanted into the inner ear to replace the missing cells, or developing therapies that will induce the inner ear itself to regrow the missing cells using the body’s normal regeneration processes. Unlike other species, such as birds or amphibians, inner ear hair cells in mammals don’t regrow when they’re damaged, so once they’re gone, they’re gone for good. The reasons for this are unknown, but it might be due to the more intricate arrangement of cells in the mammalian cochlea.
In birds and amphibians, new hair cells are generated from supporting cells, a layer of cells within the inner ear which surround the hair cells, and ‘support’ them. However, in mammals, these supporting cells appear to lose their capacity to proliferate and turn into other cell types (like hair cells) before birth. However, recent research from the laboratory of Albert Edge, at Harvard University, has found that this is not necessarily the case.
Mammalian supporting cells turn into hair cells in the laboratory
In 2012, the group published research showing that supporting cells could be grown in culture in the laboratory, and that they formed structures called ‘neurospheres’, made up of dividing cells, some of which then turned into hair cells. The source of these new hair cells was a subset of the supporting cells in which a gene called Lgr5 was activated. The Lgr5 gene produces a protein receptor on the surface of cells which interacts with particular proteins on the surface of other cells known as R-spondins. When Lgr5 and an R-spondin interact, a signalling reaction ensues involving a gene called Wnt, and this signalling leads the supporting cells to proliferate and turn into hair cells.
Lgr5 is also known to be produced by cells which can regenerate in other areas in the body, such as the intestine, and is used to identify adult stem cells. It is possible therefore, that in the cochlea, Lgr5 similarly identifies a population of cells with regenerative potential, even if they don’t necessarily use it. Not all cochlear supporting cells produce Lgr5 and it is only those that do that can turn into new hair cells.
However, whilst this happens in tissue culture dishes in the lab, there was no indication that it really happens in the cochlea until new research, published this month by the same group, suggested otherwise.
Growth of new hair cells after cochlear damage in mice
Using gentamicin, an ototoxic antibiotic which damages hair cells, the group developed a model of hair cell damage in the newborn mouse cochlea. High doses of gentamicin caused significant levels of hair cell death, but surprisingly, the researchers observed a low level of spontaneous hair cell regeneration in response to this damage. They showed that these new hair cells were derived from the supporting cells which produce Lgr5 as described above.
In addition, this group had previously shown that blocking another cell-to-cell signalling process (called Notch signalling) promoted hair cell regeneration after noise damage in adult mice and partially restored their hearing. However, they were unable to determine where the new hair cells were coming from. Inhibiting this same process in their new model of hair cell damage had a similar effect, and the group were also able to show that this hair cell regeneration was controlled by the Lgr5/Wnt signalling mentioned previously. This indicated that the Lgr5-producing supporting cells described above are indeed the source of new hair cells in the cochlea.
Now that the cells in the cochlea that can produce new hair cells after damage have been identified, and as we learn more about the molecular processes that control a cell’s destiny, it may be possible to develop therapies that can target these cells and processes to induce regeneration of hair cells in the cochlea and one day, restore hearing.
Find out more
This research was published online last month in the journal Stem Cell Reports and you can read the article here.
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