Gerbils Regain Hearing Thanks to Stem Cell Therapy

erik

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May 8, 2012
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(CBS News) Scientists have restored hearing in gerbils using a stem cell therapy that may hold promise for deaf humans.


Using human embryonic stem cells, researchers at the University of Sheffield were able to implant immature nerve cells into gerbils, which then regenerated and were able to improve hearing ability in the animals. The study was published on Sept. 12 in Nature.
According to a Nature News article on the study, more than 275 million people have moderate-to-profound hearing loss, many of whom have it caused by a disruption in communication between the inner ear and brain. Senior study author Dr. Marcelo Rivolta, a stem cell researcher at the University of Sheffield told Health Day that about 80 to 90 percent of deafness is due to problems with cells in the inner ear.

There are two types of inner ear cells. Hair cells translate vibrations into electrical signals that are transmitted via the auditory nerve to the brain. Problems with these cells are typically fixed via cochlear implant, a small device which can bypass the hair cells and directly send signals to intact auditory nerves. Neurons make up the auditory nerve, and when these are damaged, doctors have little to no treatment options available.

It's important to note that the type of deafness that the gerbils had affected only neurons, making it very rare. The Associated Press points out that type of deafness only affects between less than 1 percent to 15 percent of patients. Furthermore, the treatment won't work in all the patients with that disorder.

But, because so many disorders have to do with inner ear cell problems, the research is promising and may have future human applications.

Researchers in the study took embryonic stem cells, which can develop into any other kind of cell in the body, and grew them into a test tube that had molecules that are available when the fetus develops ears, known as fibroblast growth factors (FGFs). Some stem cells developed characteristics similar to hair cells and others turned into cells that looked like neurons.

Then the neuron-like cells, which were called otic neural progenitors (ONPs), were transplanted into the ears of gerbils that had been given ouabain, a chemical that damages the neurons in the auditory nerves but not the hair cells.

Ten weeks later, the cells had grown and some connected to the brain stem. The gerbils on average had a 46 percent overall improvement in hearing, with many of the animals registering brain activity at much fainter sounds after the transplant.

Dr. John Goddard, a neurologist at the House Clinic in Los Angeles, told HealthDay that the study was exciting because it showed stem cells helped nerve cells regrow, but added that it will take some time before it's determined if it is an appropriate treatment for human deafness. Stefan Heller, a stem-cell researcher at Stanford University in California, told Nature News it could take as long as 15 years before it is ready.

"It is clearly of interest for a lot of people because the potential is dramatic," Goddard said. "The specific article sheds additional light that there is some potential there for regrowth, or regeneration, of sensory cells. But this is going to take many years."

Prof Dave Moore, the director of the Medical Research Council's Institute of Hearing Research in Nottingham, U.K., explained to the BBC that despite the "major development," part of the difficulty with deaf patients is accessing the part of the inner ear where the problems are.

"It's extremely tiny and very difficult to get to and that will be a really formidable undertaking," he said.
 
thanks erik

but hey the researches declaration that protocols indicate a 15 year time horizon...huh

ill bet there are some people in such dire straights that they would volunteer today, to" boldly go where no one has gone before"

best wishes
mt
 
Human embryonic stem cells restore gerbil hearing

Nature
Virginia Gewin
12 September 2012

More than 275 million people have moderate-to-profound hearing loss, and many of those cases are caused by a breach in the connection between the inner ear and the brain.

Researchers have now shown how to repair a key component of that connection — the auditory nerve — by using human embryonic stem cells to restore hearing in gerbils. "We have the proof of concept that we can use human embryonic stem cells to repair the damaged ear," says lead author Marcelo Rivolta, a stem-cell biologist at the University of Sheffield, UK, whose research appears in Nature today. "More work needs to be done, but now we know it's possible."

Stem cells have been differentiated into auditory nerve cells before, but this is the first time that transplanted cells have successfully restored hearing in animals. Some in the field say that it is a pivotal step that will undoubtedly spur more research. "Research has been stymied by reviewers wanting evidence that stem cells can connect the inner ear to the central nervous system," says Richard Altschuler, a developmental biologist at the Kresge Hearing Research Institute at the University of Michigan in Ann Arbor.

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%.

Rivolta's findings — along with a study published in July showing that gene therapy can restore hearing in deaf-born mice — reinforce a spate of studies demonstrating that stem cells and gene therapy can restore sensory functions, including smell (see 'Gene therapy restores sense of smell to mice') and vision (see 'Regenerative medicine repairs mice from top to toe').

The advances are exciting, says John Brigande, a developmental biologist at Oregon Health & Science University in Portland who has a progressive form of hearing loss and is exploring stem-cell-based approaches to restore auditory function. He notes, however, that because the "exquisite architecture" of the inner ear can be damaged in many different ways, "there won't be one cure for hearing loss, there will be a variety of interventions tailored to unique conditions".

The number of people who might benefit from a stem-cell-driven increase in auditory neurons remains unclear, but stem cells could broaden the reach of existing therapies. "Because functioning auditory neurons are necessary for cochlear implants to work, stem cells open a candidate pool that cannot yet be helped," says Altschuler.

The first treatments for hearing could take at least 15 years to develop, says Stefan Heller, a stem-cell researcher at Stanford University in California who is working on other ways to differentiate stem cells into hair cells and support cells. "The next goals of any protocol are to gain higher levels of efficiency and reproducibility, determine protocol safety and confirm that transplantation leads to prolonged recovery," says Heller. "Then we can think about patients."

source: http://www.nature.com/news/human-embryonic-stem-cells-restore-gerbil-hearing-1.11402
 
I want to illustrate the significance of this study. Kuwaja and Schaettes recent paper in the last 5 years or so illustrated that tinnitus can occur with a normal audiogram. Kuwaja demonstrated loss of synaptic ribbon (which represents synapse between cochlear nerve and inner hair cells) with eventual degeneration of cochlear nerve but intact inner hair cell. Schaette demonstrated the same thing, but through ABR measurements that reflect cochlear damage.

The importance of this? Those with tinnitus and 'normal' audiogram (myself included) but with putative cochlear nerve damage/degeneration will benefit. The study shows that not only do the stem cells differentiate into a cochlear nerve neuron, but that it ALSO travels to the brain and makes the appropriate connections to restore hearing.

The caveat here is, is the plasticity changes occurring in tinnitus able to be reversed with re-afferentation? A similar study by Schaette with induced tinnitus percept through long-term ear-plug wearing demonstrated that tinnitus disappeared once participants removed the ear plug. This seems to suggest that at least in the short-term, tinnitus is reversible once we restore input. Whether this also holds true for long-term tinnitus is another question that has yet to be studied.

Conclusion: astoundingly great news for restoring hearing, super great news also for tinnitus though with some grain of salt
 
I have been always wondering, why is the theory about permanent plasticity changes within the brain so popular? There is not much evidence about it, is there? Even if it's true, I see no reason why should they be irreversible.

If I understand it correctly, the theory is that damaged hair cells put the brain in an "alert mode" and some changes within the nerves occur to compensate for the hearing loss, causing tinnitus. Difficult to express myself with my limited english vocabulary but you know what I mean.

So in theory, if stem cell injection fixes the damaged hair cells and restores hearing, wouldn't the nerves/brain just change back again to stop compensating if it is no longer needed? I believe we might soon find out...
 
Fish, no limits to your English vocab detected here, and very well explained.

I think there is a lot of rehabilitation for brain-damaged patients that relies on plasticity. Permanent plasticity therefore sounds like an oxymoron. (Like "rigid rubber" or "non-soakable sponge"). Anyway - what do I know - I'm a software developer.
 
This is old news now. From 2012! But when will we see this in human trials if it's so good?

How do they deliver the stem cells to the inner ear?
 
228573, member: 21421"]This is old news now. From 2012! But when will we see this in human trials if it's so good?

How do they deliver the stem cells to the inner ear?
The researcher talked about in this article is actually conducting a study trying to find the perfect way to deliver stem cell to the cochlea. I think it involves some kind of gel. There is a thread somewhere talking about it I think it was in late August.
 
why 15 years..?? when technolgy is going faster en faster...
we all have hearingloss...aging is losing...we need more investing people

That's the problem with the transition between experimental science and medicine, you can't really come up with an experimental solution, try it on a few animals then jump on the human subject, everything needs to be accepted by medicine institution, you can maybe volunteer to be in the first trials on humans but that's far from the being the perfect technique at the time. Some time, treatments are working but are not accepted either ethically or just methodologically and doctors won't use them to avoid any bad reputation, but that doesn't seem to be the problem here, we can only wait to see it on our local hospital.
Take care mate, we're not that far from relief.
 
They have now developed ways to get the stem cells into the inner ear. That was the biggest challenge according to the article back in 2012. Those same stem cells were from humans and would probably work better on humans than gerbils. Someone needs to open up a stem cell clinic and just offer this service. I'm pretty sure its that easy.
 

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