Developing a Safe and Efficient Way to Transport Stem Cells Into the Inner Ear

[beeeep]

Action on Hearing loss funds research on stem cell delivery.

[...]
Back in 2012, we funded Professor Marcelo Rivolta, at the University of Sheffield, as he made a huge breakthrough, showing that human stem cells could repair damaged auditory nerve cells in deaf gerbils, and even more importantly, restore their hearing. This paved the way for the development of stem cell treatments to restore people's lost hearing.

However, the use of stem cells raises some safety concerns. Stem cells, as well as being able to turn into any other cell type in the body, can also divide and replicate themselves indefinitely (this is in contrast to most cells in the body, whose growth and replication are strictly controlled). This means that they could travel beyond the site of damage in the inner ear, and more worryingly, divide uncontrollably and form tumours. It's therefore important to find ways to minimise such a risk when developing stem cell therapies.
[...]

 

[Nick Pyzik]

Action on Hearing loss funds research on stem cell delivery.

Thanks for sharing this beeeep! Any sort of hearing loss news that refers to stem cells and auditory nerve repair makes me feel more hopeful and cheerful inside.

 

[Kane Moffat]

Fantastic, this is an essential step in achieving auditory nerve regeneration, do we know when this will be ready?

 

[grate_biff]

I really hope this "gels" nicly towards a safe and viable treatment. Go Mr. Rivolta and AOHL!
Love you!

 

[Mario martz]

This is great great news!!

thanks for posting, i have a decente amount of hope on marcelo rivolta.

 

[Mricha37]

So it sounds like he has a really good idea of what he wants to do stem cell wise just needs to make sure there is no collateral damage

 

[Filip]

I'm go along with everyone else's comment and say you my hero

 

[Ears Hurt]

Amen amen amen... I can't pray enough or put magical fairy dust or whatever else needs to be done in the universe for positive results for Marcelo Rivolta!!!

 

[Pleasure_Paulie]

Just remember that stem cells is already currently available as a potential treatment for tinnitus and has yielded some anecdotal success. No treatment is 100% safe, but there is copious articles regarding the safety of stem cells after treating thousands of people for various disorders. Stories of where cancer was formed was with the use of pluripotent (embryonic) stem cells, and not multipotent which is prohibited.

I'm all for improvement in delivery of stem cells, as they have a very exciting future.

 

[Vinnitus]

I will build a Marcelo Rivolta statue with a superhero suit in my living room if he pulls this off successfully. Excellent development!

Let's hope this gel will make stem cell treatment safer and bring it to the clinic faster.

It's also a delight to read we are now more and more funding dedicated researchers to actually solve problems, instead of only funding parties who develop techniques to "manage" these problems. It makes me want to donate to AOHL...

 

[Reinier]

Let us not forget Action On Hearing Loss and people that donate to make this all possible

 

[Foncky]

I'm not sure to understand : while it's great to find ways to deliver cells into the inner ear safely, do we know yet what cells we should deliver, and how to find them in an adult body ?

 

[Reinier]

do we know yet what cells we should deliver, and how to find them in an adult body ?

When I read this: "Back in 2012, we funded Professor Marcelo Rivolta, at the University of Sheffield, as he made a huge breakthrough, showing that human stem cells could repair damaged auditory nerve cells in deaf gerbils, and even more importantly, restore their hearing. This paved the way for the development of stem cell treatments to restore people's lost hearing."
End quote.
I conclude they must know which stem cells they need and how to modify them if needed. Alos where in the body they can find these stem-cells

 

[Foncky]

Not me. Maybe this worked only with very young gerbils ? We need more details, it's promising but I don't want false hopes.

 

[Pleasure_Paulie]

Depending on the potency of the stem cell (totipotency -> pluripotent -> multipotent -> unipotent) they have the ability to become any type of cell and nerve when given to the body.

 

[Foncky]

Pluripotent are not present in the adult body, so we need the right multi or unipotent cells.

 

[Reinier]

This is an interesting read. (In my opinion).
http://www.sheffield.ac.uk/bms/research/rivolta/research

Quote: "Current developments in stem cell technology could offer new hopes for the treatment of deafness. One therapeutic approach could be to trigger sensory regeneration from existing cells or to replace lost cells by transplantation of exogenous, in vitro-maintained stem populations with the potential to produce hair cells and neurons."
And: Control animals showed no sign of functional recovery throughout the experiment. However in the transplanted animals, there was a detectable improvement in the ABR thresholds starting approximately four weeks PT. The mean auditory threshold shift, calculated as the difference between the thresholds at 10 weeks PT versus the one before onset of deafness, was of 53±1.7 dB in the control animals compared to 28.6±3.6 dB in the transplanted cohort (p 0.0002).
End quote.
I like it, I like it.

 

[Foncky]

24dB is already a huge improvement indeed.

 

[Reinier]

24dB is already a huge improvement indeed.

And that is for starters

 

[BohemianLife]

Great news. I hope we will reach results for human in short time.
Plus question : Is this therapy for just inner ear nerves ? or conclusing hair cells too ?

 

[Nick Pyzik]

Great news. I hope we will reach results for human in short time.
Plus question : Is this therapy for just inner ear nerves ? or conclusing hair cells too ?

It seems to just be focused on the auditory nerve. Or in other terms, the nerve fibers/spiral ganglion neurons that are apart of it. Usually there is a mention of inner ear cells or sensory hair cells, but there was none so in this article. Also, Marcelo Rivolta had been previously working on a study with gerbils using stem cells to repair their damaged auditory nerves. So it would be assumed that the focus is only on stem cells and deafness/hearing loss due to "auditory neuropathy".

 

[Anonymous2929]

I always had my money on Rivolta and Action on Hearing Loss. No one else has done so much in Britain than these two in terms of funding and research.

This gives hope to me and other people suffering from profound/severe hearing loss.

On the bright side, I live an hour away from Sheffield and maybe Rivolta will dose me if asked him nicely!

 

[Mario martz]

@bill 112

 

[Reinier]

Plus question : Is this therapy for just inner ear nerves ? or conclusing hair cells too ?

How I read it, haircells too.
www.sheffield.ac.uk/bms/research/rivolta/research
Quote: Almost 90% of people affected suffer a sensorineural deficit, which involves loss of the two first cells in the auditory pathway: the sensory hair cells and their associated auditory neurons.
Also: we expanded a population that expressed stem cell markers such as NESTIN, SOX2, OCT4 and REX1 and have the ability to differentiate into functional sensory neurons and hair cell-like cells. These cells are an excellent system to study human ear differentiation and allowed us to define a media to sustain stem cell growth as well as conditions to induce the differentiation into neurons and hair cells.
There are more references to haircell regeneration in this article, but this is getting way too complicated for me.
Interesting is when it is pointed out that regenerating the two first cells in the auditory pathway could return hearing.
That is how I read it. That makes it sound less complicated, but unfortunately this is not so.

 

[spingee]

Maybe one day i will be happy like this guy

 

[Ian Mac]

Yes please my hair cells are doing okay but my auditory (vestibucochlear) nerve is not happy! In fact I hear it crying.

There won't be a treatment for tinnitus that doesn't involve every part of the disorder (ears, brain, body posture, bacterial and vital and fungal damage). Doctors can't have a treatment that works for some people and not others because of how medicine is regulated in USA, We need a cure all, so the tinnitus treatment will need to regenerate and nourish each and every part of the auditory system. Ie. The 8th cranial nerve, the hair cells, and perhaps the part of the brain that processes sound will all need to be addressed for a approved T cure... Yikes!

 

[Nick Pyzik]

How I read it, haircells too.
www.sheffield.ac.uk/bms/research/rivolta/research
Quote: Almost 90% of people affected suffer a sensorineural deficit, which involves loss of the two first cells in the auditory pathway: the sensory hair cells and their associated auditory neurons.
Also: we expanded a population that expressed stem cell markers such as NESTIN, SOX2, OCT4 and REX1 and have the ability to differentiate into functional sensory neurons and hair cell-like cells. These cells are an excellent system to study human ear differentiation and allowed us to define a media to sustain stem cell growth as well as conditions to induce the differentiation into neurons and hair cells.
There are more references to haircell regeneration in this article, but this is getting way too complicated for me.
Interesting is when it is pointed out that regenerating the two first cells in the auditory pathway could return hearing.
That is how I read it. That makes it sound less complicated, but unfortunately this is not so.

Thanks for also posting this segment, Reinier.

I still don't understand at all how there are researchers, Rivolta and his team for example, who have found a connection between sensory hair cell loss and hearing loss. But then another team of researchers, like Charles Liberman, have found no results of sensory hair cell death connected to acoustic traumatized hearing loss? Am I the only one who is very puzzled by that?

It's one of the biggest questions I wish I could get answered about what's happened to my hearing. Sensory hair cell loss just doesn't add up with how I've been able to pick up sounds. Major changes in my hearing ever since last fall.

 

[Mario martz]

I wonder if this possible treatment would also work for people with menieres.

 

[Aaron123]

I still don't understand at all how there are researchers, Rivolta and his team for example, who have found a connection between sensory hair cell loss and hearing loss.

There's nothing novel about this. Hair cell loss is the primary cause of observed (as opposed to "hidden") hearing loss. (That said, I don't think Rivolta and colleagues are particularly focused on hair cell death. To the best of my knowledge they have not been successful in generating functional hair cells.)

But then another team of researchers, like Charles Liberman, have found no results of sensory hair cell death connected to acoustic traumatized hearing loss?

The noise level and duration were chosen so as to cause temporary but not permanent threshold shifts: "We adjusted the sound level and duration of an octave-band noise exposure to produce a moderate, but reversible, threshold elevation" (pg 14079; Kujawa and Liberman 2009).

Rivolta's work being referenced is primarily Chen et al (2012) in Nature. They looked at an animal model of auditory neuropathy. Like Kujawa and Liberman, their approach preserved the hair cells but unlike Kujawa and Liberman, they killed about 95% of the SGNs : "Application of ouabain directly to the round window selectively damages the type I SGNs, preserving the hair cells and the organ of Corti 26 (Supplementary Fig. 10). After ouabain application, only a small number of SGNs survived (6.4%; see Supplementary Table 11)" (pg 279; Chen et al. 2012). In contrast, Kujawa and Liberman report a worst case survival rate of about 50% of synapses at high frequencies (pg 14082).

So it is a difference between about 6% of SGNs being functional vs. about 50%. Even the 50% loss in Kujawa and Liberman does not result in noticable threshold shifts because of other compensation: "Thus, diffuse loss of half the cochlear nerve and the resultant 50% decrease in response amplitude, can be compensated either by doubling the discharge rates in remaining neurons or doubling the number of neurons responding. Either of these compensatory increases is accomplished with only a few dB increase in stimulus level..." (pg 14082). Thus, it takes a tremendous loss of SGNs (or the ribbon synapses) to cause a significant across the board increase in hearing thresholds as seen in Chen et al. (2012). The damage must be so extensive that it is not possible to increase the discharge rate or other functioning neurons by enough to compensate.

So the purposes of the papers and thus the set-ups are completely different. Kujawa and Liberman (2009) show that noise levels below which hair cell death occurs have consequences for hearing - though not for thresholds. Chen et al (2012) are able to use human embryonic stem cells to restore SGN function in an animal model of auditory neuropathy (drug rather than sound induced). Neither paper involved hair cell loss, and neither finding contradicts the other.

 

[Reinier]

(That said, I don't think Rivolta and colleagues are particularly focused on hair cell death. To the best of my knowledge they have not been successful in generating functional hair cells.)

@Aaron123 Thanks for the comprihensive post.

So neuropathic deafness does not include hair cells? It is the neurons (ganglion neurons) that are lost?
The improved ABR threshold shift they mention is because of synaptic reconnecting and Ganglion neurons regeneration?
They do mention hair cell-like cells, which are not actual hair cells. I assume this is important because hair cell-like cells could become functioning hair cells.
So many questions. I will just continue to read and take in information. Eventually over time (years) I will understand more about my hearing than any other part of the body