Why don't hair cells heal themselves like cuts and scrapes do? Will we have solutions to this soon?

by Uncle-Dads-Whistle

I work on the development of neurosensory cells in the cochlea, with the goal being figuring out the secret to hair cell regeneration.

Mammals have lost the ability to regenerate hair cells (the types of cells that translate sound waves into a neural signal) after damage. Birds and reptiles, however, have maintained that ability, and after enduring trauma or infection, or drug-induced hair cell loss, a non-sensory supporting cell will transdifferentiate (change from one differentiated cell type to another) into a mechanosensory hair cell. Why exactly can't mammals do this? Well, we're not exactly sure. There are all sorts of inhibitory signals within the mature mammalian cochlea that prevent cell division or transdifferentiation (which is also one reason why we never see any cancer in this system; the body basically has all the proliferation completely shut off). So we try to figure out if there are ways around this apparent moratorium on proliferation/differentiation in mammalian cochleae, and if there's a way to open up the possibility of regenerating hair cells in mature mammalian cochlea.

With gene therapy or viral vectors, we have been able to grow hair cells in vitro. That's true, in fact it doesn't even take anything that complicated to grow hair cells in culture - you just need to dump atoh1 protein (the master gene for hair cell development) on some competent cells and they will turn into hair cells (they'll even recruit neighboring cells to become supporting cells). But that doesn't really help us regenerate hair cells in mature mammalian cochlea - those cells aren't really competent to respond to that signal once they're past a certain point. There's been a few studies that have succeeded in generating transdifferentiated hair cells from support cells using genetic systems to overexpress those genes that direct a hair cell fate - but this only lasts about a month after birth before you start losing that effect. And on top of that, the functionality of the hair cells that were generated was questionable. And of course, these animals were genetically engineered to have these genes turned on at certain points, this is obviously not a viable option to translate into human treatment.

So it still remains that gene therapy is probably our best shot to regenerate hair cells in a mature human cochlea. The only problem is we don't know exactly what combination of genes will do the trick on a mature cochlea. So a lot of work is done on figuring out how this happens normally, then trying to find a way to manipulate that system. Since this is my field, I could go on forever about this, but I don't want to start getting too tangential or far out, especially since I don't have time to look up sources (gotta go work on some of my mice right now) but if y'all have any questions I'll do my best to answer them when I get a chance.