Stem Cell Secretome Treatment

I wanted to start a new thread specifically on Stem Cell Secretome (SCS). It is a Stem Cell-based regenerative treatment, but without the cells themselves (using their secreted factors instead).

Cell Secretome: Basic Insights and Therapeutic Opportunities for CNS Disorders:
The term secretome was introduced by Tjalsma et al., who defined it as “both the components of machineries for protein secretion and the native secreted proteins”. This definition then evolved to a more elaborated concept by Hathout and Agrawal in which the secretome was defined by the factors that are secreted by a cell, tissue, or organism to the extracellular space under a defined time and conditions. Currently, this definition could be updated since it is known that, beyond soluble factors, the secretome also has the presence of lipids and extracellular vesicles (EVs) carrying important molecules.

Especially interesting is this:

Based on the cited studies, it is clear that there is increasing evidence that stem cell secretome can have neuroprotective, neuroregenerative, and immunomodulatory actions. Many studies support the conclusion that the recovery of neural and glial function in CNS trauma and disorders is due to the secretion of soluble factors and vesicles by the transplanted MSCs rather than by cell replacement.

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.

Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo:
The present study provides initial proof of the high potential of UC-MSC-derived EVs to support neuronal survival and to repair noise-induced damage in the inner ear. The capacity to manufacture and characterize clinical-grade EVs under current GMP will support the rapid translation of these research findings into clinical application and may be helpful also for the intervention in other organ systems and disease indications. Even though more research into the mechanism of action of MSC-EVs is needed, our data indicate that clinical grade EVs derived from UC-MSC are highly protective for auditory neurons and can protect the inner ear against noise trauma in vivo. These findings provide a solid foundation for the future use of human stromal cell-derived EVs as a novel cell-free therapeutic approach for the protection of the inner ear.

Some more review articles below. They do not specifically mention hearing loss or tinnitus, but they do talk about the neuroregenerative effects of SCS.

The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration

The Emerging Role of Exosomes in the Treatment of Human Disorders With a Special Focus on Mesenchymal Stem Cells-Derived Exosomes

This clinic is offering Secretome treatment in Germany:
https://anova-irm.com/en/stem-cell-therapy/secretome-exosomes-therapy

My thinking is (and please correct me if I am wrong! I am a physicist by training so this is definitely not my area) that for cochlear synaptopathy, growth factors released by the stem cells should be the therapeutic agent. In addition, cell-free treatment is supposedly safer. I have 10+ tinnitus noises, hyperacusis and auditory neuropathy (probably just synaptopathy, but they diagnosed it as 'neuropathy' using ABR). It's all a result of two recent acoustic traumas. I have no hearing loss in my audiograms, except for 30 dB at 16 kHz. Otoacoustic emissions normal.

I am having a Skype call with ANOVA IRM this Friday. If all goes well, I will be going for my liposuction in November and Secretome treatment in December. From one adipose tissue sample (10 ml) they can produce 10 doses of Secretome. It can be frozen and stored for up to 2 years, so you can repeat the treatment without the need for harvesting adipose tissue again. They do IV administration, but I will ask for trigger points/intranasal, too. Exosomes (small lipid NPs containing proteins and miRNA) do cross the BBB, so do BDNF and NT3, in smaller quantities, so I hope IV can be sufficient. In the basic treatment plan, they include 1 liposuction, cell separation, growth, Secretome extraction and 3 treatments. The cost is around €20,000 EUR.

I will keep updating this thread with my progress. In the meantime, does anyone have any thoughts about this kind of treatment? I understand that this is more of a shotgun-approach to see what sticks.

 

Skype call done:

• They have not had any hearing loss patients.
• They have had good success with ALS - stopping or slowing down the progression, while the patient keeps receiving the Secretome every few months.
• They assured me that BDNF and NT3 from the IV-injected Secretome cross the BBB. (? - I will do more research)
• They can also apply the Secretome intranasally, if I so wish.
  
• In their opinion, it does have some chance of working, especially in cases like mine where the patient has neuropathy and no/little IHC damage.
• Their patients have never had any serious side effects.
• The patients do not need immunosuppression for the procedure.
• The cost is €19,500 (3 x 7.5 ml Secretome doses), and you can purchase 7 additional ones, costing about €2,150 each.

I am willing to try this, so I have reserved a slot on the 6th of December. They may get more staff on board soon and in that case my slot will move up. I will update this thread accordingly.

 

Good luck man, too bad they are not guaranteeing anything for that big price.

 

You are doing everybody who’s considering it a huge favor by going ahead with this. Crossing my finger for you.

 

A minor correction - the mini-liposuction will harvest 30-200 ml of fat (I previously thought it would be 10 ml).

I guess I need to gain weight? I have like 10% body fat.

 

Please keep us updated, thanks!

 

Hi Tau,

Calling it a shotgun-approach is spot on in my opinion.

A couple of Tinnitus Talk members have tried stem cell therapy with decent results. They weren't entirely cured, but the tinnitus did get better.

One of them, attheedgeofscience, went to Stemcells21 in Bangkok. He used donated stem cells. The treatment, if you are doing it today, costs $38,000 USD.

Another, whose alt I don't recall at the moment, went to a clinic in Australia. Not for her tinnitus, but for some other condition. She used her own stem cells, extracted by liposuction. I researched the doctor, and he's a gold digger with an ugly record. The treatment improved her tinnitus just the same.

There's also a couple of Tinnitus Talk members who tried stem cell therapy with no or uncertain results.

The bottom line is that if you want relief from this terrible condition, stem cell treatments is really the only place to go. Your attempt is interesting, because:

1. Germany isn't that far away for many of us.
2. The cost - €19,500 EUR - is relatively cheap, assuming the treament itself is of high quality.

I wish you the best of luck and look forward to your updates. The more people who try stem cells and share their experiences, the more we learn. It will likely take about three months for the results, if any, to show themselves.

 

Thank you! The approach is also interesting because the IV injections are cell-free, and therefore safer. I think I am more worried about the liposuction than the actual treatment as I have very low body fat.

Germany is close, true, but there are other close clinics, too, like Swiss Medica in Russia. I recall reading about one member of Tinnitus Talk going there and seeing little to no improvement. I believe their treatment would be cheaper than this one. SC21 in Thailand have treated more hearing loss patients, so they are my second choice.

I would mainly like to fix the reactivity. Yesterday I had an episode of fleeting tinnitus, and during that episode, running my hand across the bedsheets made loud metallic noises in my left ear. If this is a preview of what is to come, I want to stop and/or somewhat revert the neuropathy at any cost.

 

@Tau, you might want to try an SSRI for you reactive tinnitus. I had quite good results with it. Both in the aspect of lowering the reactive part but also not to panic/and overfocus on the distorted part. With my recent setback I am going up in dose again. Once I feel better, I will slowly taper them out. So far I have tested Escitalopram or Citalopram. Quite similar.

Didn't we just recently have a Dr. with quite good results from SSRI?

SSRI should be very safe and been on the market for a very long time.

 

Tinnitus can be quite the agonizing condition. Severe symptoms are unlikely to go away by themselves. If you're determined to get relief and can afford stem cells, then you just have to go for it and hope it works.

I can't assess the scientic aspects of different treatmenst very well, but if the protocol Anova uses works against ALS, then I see no reason to why it shouldn't have a chance to work against tinnitus as well. A significant effect would be major news.

 

@Tau, do you know why the no IHC damage is a factor? If this shows any signs of success, I'll be very interested to pursue but, in addition to sharing many of the symptoms you describe, I do have hearing loss.

 

My thinking is that repairing synapses requires neurotrophic factors (Liberman's research with mice - injecting NT3 into their cochlea after noise trauma restored synapses). Otonomy are using BDNF in OTO-413, etc. But I have not seen research showing that neurotrophic factors can regenerate IHCs - maybe they can? Stem cells have been shown to improve hearing thresholds in animal models, but then the question remains if it's a result of the cells or their secretions.

Though I would still try it even if I had IHC loss (dips in audiogram). I do have hearing loss, it's just that my thresholds are almost intact. Drum plates in music crackle and hiss, but hey, I can hear that pure tone!

 

I had liposuction (stomach through my belly button) stem cell intratympanic injection in May but no improvement at Broward ENT in Fort Lauderdale in Miami in. May 2021. The cost was $7000.00 USD. I'll keep trying though maybe Next stop is Dr. Mimbo Shim in South Korea as soon as their COVID-19 situation gets more under control. Or maybe StemCells21 in Thailand. Money is no issue. I need some improvement. Begging for it...

 

Was it one injection? Do you have tinnitus or hearing loss, too?

Thank you for the info, I was just looking at their clinic.

 

Two separate injections from both blood and fat cells, lipo from my stomach and blood withdrawal from my arm. I have high frequency hearing loss (-50 dB @ 4000 Hz, -60 dB @ 4000 Hz, -55 dB @ 6000 Hz & -30 dB @ 8000 Hz.

I got a very loose eardrum from an ear surgery. I had the surgery on 7/2020 (which caused my hearing loss), before that I just had tinnitus in my right from being slapped in the ear. A Dr. at Mass eye & ear recommended middle ear exploration, it didn't work out. It screwed my life up very badly.

I think I have PET also. I'm hopefully seeing Dr. Poe soon for a consultation. Maybe he can help me but I suffer everyday. It's very weird, I can get my hearing back to almost normal by doing a Valsalva maneuver but only for maybe up to an hour, then it goes back to its stable bad state.

 

Does anyone know if this could work for hyperacusis also? Or anyone tried it, at least? Thanks.

 

I have hyperacusis, too. So I will let you know. Basically at the end of every day my ears feel pressure and hurt a bit. This was not immediate - after my initial trauma in June I was fine with sounds (I only had high frequency sounds feel louder than usual, but I had very little ear discomfort compared to now). I started getting ear discomfort in July and then my MRI in August absolutely DESTROYED my ears - crinkling paper is uncomfortable now. Strangely enough, stuff like traffic noise etc. outside does not feel too loud at all. MRI did not feel too loud (I would have stopped it otherwise).

Some good news: my liposuction has been moved to October!

I am unsure as to what I will do if this treatment does not help.

 

Ah, are your doctors sure it's sensorineural hearing loss? Could it be conductive and that's why the stem cells did not help? Because doing a Valsalva maneuver should not bring back your hearing if your cochlea is damaged.

I didn't know 4 kHz was considered high frequency to be honest, my initial injury killed my 12-16 kHz range.

 

Have you talked to any other doctors about this? I’m wondering if anything can be done to stabilize the eardrum. It sounds like it’s too loose now and causing the HL. Can they possibly reinforce it or rebuild it? Maybe Hain or Djililian could help with a diagnosis and treatment?

 

It's possible if you have Eustachian tube problems...

 

I don't see how stem cells or their secretome could fix Eustachian tube problems. What would be the mechanism?

 

I think they could really help by fighting inflammation.

 

Would steroids not help instead?

 

They usually do but temporarily in most cases. I would imagine SCs are more permanent or could give enough time for the healing to take place.

 

Hi Scotty,

In your situation, I would consider to consult a second ear surgeon about the side effects from the surgery you had last year. Why has the eardrum gotten loose and why did it cause tinnitus? Something sure sounds to be anatomically off if you can temporary restore your hearing with the Valsalva maneuver.

Dr. Minbo Shim injects stem stells through the eardrum. I wonder if that would be safe in your case. If stem cells is the solution to your problem, StemCells21 might be a better option.

It's just incredible how screwed up life can get.

 

Makes sense in that case. They don't really help me that much.

 

I don't know, but increasing pressure in my middle ear brings my hearing back to normal. I had tinnitus before the surgery.

 

Who are these names you mentioned? It's a possibility. My eardrum is extra loose; lots of movement.

 

Looks like your hearing loss is possibly fixable then - it's not the inner ear that's causing it.

 

They are probably the most respected neurotologists in terms of inner/middle ear diagnosis and treatment.