Stem Cell Secretome Treatment

[ploughna]

@Tau, if I thought this had a decent chance of helping with low risk, I'd be right in line after you to try it.

Do you (or anyone else reading) have any other verifiable success, or partial success, stories? I've read the @attheedgeofscience thread, but that was ~8 years ago, and can't find any other reports. You'd think there'd be some information out there at this point. I realize deep pockets are needed but I know I'd literally pay anything to improve my situation - and I know from spending time on this forum, plenty of others the same!

 

[Tau]

@Tau, if I thought this had a decent chance of helping with low risk, I'd be right in line after you to try it.

Do you (or anyone else reading) have any other verifiable success, or partial success, stories? I've read the @attheedgeofscience thread, but that was ~8 years ago, and can't find any other reports. You'd think there'd be some information out there at this point. I realize deep pockets are needed but I know I'd literally pay anything to improve my situation - and I know from spending time on this forum, plenty of others the same!

In this thread you will find the usernames of 3 or 4 people who benefitted from stem cells:

https://www.tinnitustalk.com/threads/choice-of-stem-cells.37721/

There were also a couple who had no effect on their tinnitus.

I am doing secretome treatment because it's a lot safer and I have nothing to lose but money. No one, as far as I know, has done it for hearing disorders, but the research and reasoning behind it is sound when it comes to nerve repair.

My date has been moved to the 18th of October for the liposuction. The secretome will be ready 4 weeks after that.

 

[Tau]

Exosomes from human adipose-derived stem cells promote sciatic nerve regeneration via optimizing Schwann cell function

"In conclusion, we demonstrated that ASC‐Exos could facilitate axon
regeneration and myelination, and thus accelerate sciatic nerve
regeneration in rats. ASC‐Exos mainly optimize SC function to promote
nerve regeneration. After being internalized by SCs, ASC‐Exos promoted
SC proliferation, migration, myelination, and secretion of neurotrophic
factors by increasing the expression of corresponding genes. At the same
time, neurotrophic factors further induced axonal regeneration. The
endogenous SC myelination was also accelerated after ASC‐Exos
stimulation. Thus, our results demonstrate that ASC‐Exos could be a
novel treatment paradigm for peripheral nerve regeneration."

And this is a good review of ADSC and their exosomes:

Fat Therapeutics: The Clinical Capacity of Adipose-Derived Stem Cells and Exosomes for Human Disease and Tissue Regeneration

 

[ploughna]

@Tau, that's very helpful, even though I don't think I understand half of the technical details! One aspect I wondered about is how the stem cells can make their way to the cochlea via this method whereas other research is focused on direct to the cochlea delivery methods (e.g., Rinri Therapeutics).

Please do keep us posted on your progress.

 

[Vincent R]

My date has been moved to the 18th of October for the liposuction. The secretome will be ready 4 weeks after that.

 

[Tau]

@Tau, that's very helpful, even though I don't think I understand half of the technical details! One aspect I wondered about is how the stem cells can make their way to the cochlea via this method whereas other research is focused on direct to the cochlea delivery methods (e.g., Rinri Therapeutics).

Please do keep us posted on your progress.

That is actually a good question. In mice stem cells have been shown to improve hearing when injected intravenously, and there was also that one study with 11 children with hearing loss, half of whom improved after IV stem cell administration (I believe I posted links to these studies in my original post). Apparently some stem cells do cross the BBB, but in small quantities.

However, exosomes and growth factors do cross the BBB (this study mentions that), and some researchers think these secreted factors are responsible for the regenerative effects and not the cells themselves (link). I will post more research when I am not on my phone. The gist is that the secreted factors can induce neuritogenesis.

It is a shot in the dark with this treatment, though, because you need high concentrations of these neurotrophins, growth factors and exosomes, and IV delivery is not ideal, as you said yourself. However, even a small improvement would increase my quality of life by a huge degree, so I am willing to try this treatment. In addition, Anova agree to do intranasal administration, too, so I may try both IV and that. Moreover, since my trauma is recent, I think I've lost the synapses connecting the IHCs to SGNs, and not the SGNs themselves, so promoting synaptogenesis instead of replacing the neurons should theoretically be sufficient (like in Liberman's mouse model with NT-3).

Of course, I will keep updating this thread.

 

[ploughna]

Understanding it's a 'shot in the dark' as you put it no matter what, I wonder what the therapeutic window does look like over time? It's almost a year since the acoustic trauma that sent me from moderate to severe. I did reach out to Anova last week but simply got an auto-reply email saying I'd have to wait for a reply due to their backlog.

 

[Tau]

They will reply eventually. They don't offer this treatment for conventional hearing loss, though: they've only agreed to take my case because I have no pure tone threshold change, no otoacoustic emission change, but my ABR shows some neuropathy.

I think something like SC21 mesenchymal stem cells is a better choice if you have hearing loss that shows up on an audiogram.

I wonder what the therapeutic window does look like over time?

According to Liberman's research: "The primary degeneration of cochlear nerve synapses will eventually lead to death of the spiral ganglion cells in the absence of intervention1, however, the death of the cell body and central axon takes months to years1, during which time the neurons likely remain electrically excitable, given that cochlear implants continue to function for years after hair cell loss. Thus, there may be a long therapeutic window within which to regenerate the peripheral axons and/or synaptic connections in cases where the hair cells remain intact."

 

[Tau]

@ploughna, have you got a response from Anova? I have already booked my flights.

 

[scotty03874]

@ploughna, have you got a response from Anova? I have already booked my flights.

Where are they located and how much does it cost per ear?

 

[Tau]

Where are they located and how much does it cost per ear?

This is intravenous, the cost is €20k for 3 doses, that includes adipose tissue harvesting, cell separation, expansion, secretome collection and storage for 2 years.

They are in Germany. It's not a treatment for hearing disorders specifically, but it has shown good results in neurodegenerative cases, and since I have cochlear neuropathy, I am willing to try it.

 

[ploughna]

@ploughna, have you got a response from Anova? I have already booked my flights.

No - nothing yet. I may just try a direct phone call this week rather than email.

 

[Tau]

I found this very interesting:

Human mesenchymal stromal cell therapy for damaged cochlea repair in nod-scid mice deafened with kanamycin

Both adipose tissue SCs and bone marrow SCs "engrafted in the cochlea of damaged mice, inducing regeneration of the damaged sensory structures".

What's relevant to this thread:

"However, the number of hybrid cells detected in the cochlea was apparently low and absent in OC (*organ of Corti*), where regeneration was documented, similar to what was previously described. These data suggest that human MSCs do not directly replace lost cells but exert their regenerative potential mainly through paracrine effects, probably by secreting trophic and antiapoptotic factors inducing the recipient cells to recover damage. This hypothesis is supported by previous data on a myocardial infarct model, in which injection of conditioned medium collected from hypoxic Akt–MSCs significantly limited infarct size, improving the cardiac performance".

If this works similarly in humans, the secretome may really be a viable treatment. 5 weeks left until I get my liposuction!

 

[ploughna]

Fingers crossed! Wishing you the best of luck with this.

 

[Suaimhneach]

Best of luck. I hope it goes well. Keep us updated!

 

[scotty03874]

I found this very interesting:

Human mesenchymal stromal cell therapy for damaged cochlea repair in nod-scid mice deafened with kanamycin

Both adipose tissue SCs and bone marrow SCs "engrafted in the cochlea of damaged mice, inducing regeneration of the damaged sensory structures".

What's relevant to this thread:

"However, the number of hybrid cells detected in the cochlea was apparently low and absent in OC (*organ of Corti*), where regeneration was documented, similar to what was previously described. These data suggest that human MSCs do not directly replace lost cells but exert their regenerative potential mainly through paracrine effects, probably by secreting trophic and antiapoptotic factors inducing the recipient cells to recover damage. This hypothesis is supported by previous data on a myocardial infarct model, in which injection of conditioned medium collected from hypoxic Akt–MSCs significantly limited infarct size, improving the cardiac performance".

If this works similarly in humans, the secretome may really be a viable treatment. 5 weeks left until I get my liposuction!

I did liposuction stem cells in May 2021. Three injections in Fort Lauderdale, FL. It didn't do anything to help my hearing loss or tinnitus... FYI.

 

[Tau]

I did liposuction stem cells in May 2021. Three injections in Fort Lauderdale, FL. It didn't do anything to help my hearing loss or tinnitus... FYI.

I remember. This is a bit different because they will expand the cells and stimulate them to secrete growth factors and exosomes. And only then, 4 weeks later, will they separate the secretome and inject it.

 

[scotty03874]

I remember. This is a bit different because they will expand the cells and stimulate them to secrete growth factors and exosomes. And only then, 4 weeks later, will they separate the secretome and inject it.

Best of luck... I hope it helps.

 

[Tau]

Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice

Abstract
Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 μg/μL) injection at the same time point; and (ii) UCMSC exosome (1.2 μg/μL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.​

Both intraperitoneal and round window injection of UCMSC exosomes showed protection against hearing loss, but the effect was bigger when they used RWI.

 

[Lukee]

Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice

Abstract
Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 μg/μL) injection at the same time point; and (ii) UCMSC exosome (1.2 μg/μL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.​

Both intraperitoneal and round window injection of UCMSC exosomes showed protection against hearing loss, but the effect was bigger when they used RWI.

This is interesting. Strange that intraperitoneal has any effect at all but it's clear that RWI is much more potent. I wonder if IT would be just as good or at least better than IP.

It seems though that this study mostly refers to oto-protection and repair and cannot regenerate dead hair cells. I still think it's a step in the right direction. Hopefully they can get some human trials going.

 

[Tau]

This is interesting. Strange that intraperitoneal has any effect at all but it's clear that RWI is much more potent. I wonder if IT would be just as good or at least better than IP.

It seems though that this study mostly refers to oto-protection and repair and cannot regenerate dead hair cells. I still think it's a step in the right direction. Hopefully they can get some human trials going.

They speculate it's both protection and partial regeneration.

Intraperitoneal reduced the threshold at 12 kHz from 60 dB to 40 dB, RWI reduced it from 60 dB to 20 dB, both are significant.

 

[Lukee]

Would additional injections increase the outcome?

 

[Tau]

Would additional injections increase the outcome?

Good question, I would also like to see a study where they administer exosomes or stem cells something like a month after the injury.

I guess I will report back on my own experience in a few months.

 

[AVIYT]

I'm currently saving up money for stem cells. I was inspired by @attheedgeofscience's posts last year. My tinnitus is getting worse, but mentally I'm okay I guess...

Working hard to try stem cells in 2023-2024. The $20k cost is not great, hopefully it gets cheaper in the future.

 

[Tau]

I'm currently saving up money for stem cells. I was inspired by @attheedgeofscience's posts last year. My tinnitus is getting worse, but mentally I'm okay I guess...

Working hard to try stem cells in 2023-2024. The $20k cost is not great, hopefully it gets cheaper in the future.

I think you can get cheaper treatment in Mexico, but it depends on the kind of SCs you want to get and whether you trust the clinic.

 

[Lukee]

Good question, I would also like to see a study where they administer exosomes or stem cells something like a month after the injury.

I guess I will report back on my own experience in a few months.

Hey @Tau, when are you scheduled for your liposuction?

 

[AfroSnowman]

I'm currently saving up money for stem cells. I was inspired by @attheedgeofscience's posts last year. My tinnitus is getting worse, but mentally I'm okay I guess...

Working hard to try stem cells in 2023-2024. The $20k cost is not great, hopefully it gets cheaper in the future.

How much and where is your hearing loss? I know I've come across @attheedgeofscience's story before but I don't recall if he had notable hearing loss or if the steam cell treatment just cured the tinnitus alone. Do you know?

 

[Tau]

Hey @Tau, when are you scheduled for your liposuction?

Checkup on the 18th, liposuction on the 19th.

 

[Lukee]

Checkup on the 18th, liposuction on the 19th.

Fingers crossed.

 

[Toby1972]

@Tau, the experiment sounds totally experimental. Please report in December. I'm interested in the topic. I'm back at the point where I would try anything. The €19,500 would be well worth it to me, I can simply use an intraday profit with BioNTech shares for it