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Author Topic: Where to get cultured stem cell procedure?  (Read 14506 times)

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Offline db1984

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Re: Where to get cultured stem cell procedure?
« Reply #45 on: July 29, 2020, 09:51:15 AM »
Hi mang0954,

The electrical stimulator is a Compex Edge. I've been using it for a few weeks and so far I'm impressed:

https://www.compex.com/compex-edge-2-0-muscle-stimulator-kit-with-tens

I decided to get it after reading multiple articles about how it's impossible to isolate the VMO through exercise alone, but that electrical stimulation can effectively isolate it. The goal of this is to improve my patellar tracking as much as possible:

http://www.viviangrisogono.com/knee/ems-for-vmo
https://spinalflowyoga.com/exercise-wont-selectively-activate-the-vmo-but-electric-stimulation-will/
https://www.academia.edu/38834008/The_Effect_of_Exercise_and_Electrical_Muscle_Stimulation_on_the_Architecture_of_the_Vastus_Medialis_Oblique_-The_Empi_Electrotherapy_System
https://www.researchgate.net/publication/280236807_Effects_of_electrical_stimulation_of_vastus_medialis_obliquus_muscle_in_patients_with_patellofemoral_pain_syndrome_An_electromyographic_analysis

My idea to try ultrasound is based on the studies listed below. These are from a research group at the University of Nebraska that derived a resonant frequency for chondrocytes and MSCs at 5 MHz. I should clarify that these aren't human trials but purely scientific studies in the lab. In my opinion, the most convincing work they've done is repairing cartilage fissures in osteochondral explants, just by applying ultrasound. They've also shown that they can use ultrasound to enhance chondrogenic gene expression in MSCs, so "in theory" you could enhance the outcome of a stem cell injection with ultrasound. This is very impressive in my opinion and the basic science makes sense, but how well this will translate to an actual knee hasn't been demonstrated in human trials.

This is definitely a grey area that I'm willing to try myself but wouldn't recommend to others. For my day job I'm an engineer at a company that makes medical ultrasound probes. I know how to fine tune them to keep the power levels safe, in fact that's what I do at my job. The probes that they're using in these studies aren't medical grade probes but are normally used in industrial applications. They should be safe if the power output is kept low. There are no FDA approved therapeutic ultrasound systems that I'm aware of that put out the same frequency and power levels used in these studies, hence my need to do my own experimentation. While I consider using ultrasound probes on my knee to be low risk, It is possible to hurt yourself with these probes if you don't know what you're doing. This is why I can't specifically recommend this to anybody else, although I'm willing to share what I'm experimenting with. Anyways, here's the studies I mentioned. They give a detailed description of the ultrasound setup they used:

https://pubmed.ncbi.nlm.nih.gov/31054572/
https://pubmed.ncbi.nlm.nih.gov/31190618/
https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1532-2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684760/

I would definitely recommend trying Regenexx-C. It's very safe, non-invasive, has a lot of efficacy and doesn't burn any bridges. They have demonstrated repair of cartilage defects with their injection technique, although it seems to work best in small defects and not in all patients. I think with enough optimization I can get better results with cartilage repair, which is why I'm researching all this stuff. I'm not quite ready to give up on it yet, so when the time comes I'm going to try again, probably some time in 2021.

By the way, if you want to try Dr. Saw's procedure I'm pretty sure it will be a lot more than a few weeks in Malaysia. Isn't it multiple injections spread out over months? I know that's how Dr. Broyles is doing it in the US, although I could be mistaken.
« Last Edit: July 29, 2020, 09:58:21 PM by db1984 »
2016: Patellofemoral OA, Lumbar DDD
2017: Regenexx-C both knees and lumbar spine
2018: 2nd Regenexx-C treatment
2020: Left knee arthroscopy, intra-osseous plus intra-articular PRP, cartilage ultrasound stimulation
2021: Got some new cartilage on my MRI!

Offline Nici_j

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Re: Where to get cultured stem cell procedure?
« Reply #46 on: September 28, 2020, 10:05:12 AM »
Hi there - I've been reading your posts with interest as I seem to have similar knee issues - small 3 mm diameter full thickness lesion in trochlear groove with subchondral oedema. It's a trauma injury from 6 months ago when I had to jump a fence to escape some young cows running towards me and I caught my foot in the fence as I jumped down and twisted my leg. I've only just got the diagnosis from MRI and looking into what I can do next. I'm pretty sure that the pain I am getting is from the oedema. I'm also concerned that if I don't manage to find a way to heal the lesion, that I'm always going to be susceptible to oedema. I'm probably going to try stem cells but I am also looking at extracorporeal shockwave therapy for the oedema and wondered if you had looked into that or considered it at all? It seems to be quite successful.

https://pubmed.ncbi.nlm.nih.gov/29384878/

Offline db1984

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Re: Where to get cultured stem cell procedure?
« Reply #47 on: December 09, 2020, 11:47:50 AM »
Nici_J,

Sorry I didn't reply sooner, I haven't been on the site in a while. Check out my recent reply in the "Any recent stem cell experience" thread:

https://www.kneeguru.co.uk/KNEEtalk/index.php?topic=78021.0

3 mm is pretty small but the edema is more concerning, it's important to treat that to prevent further cartilage loss. You might try getting an intra-osseous injection of PRP or BMAC. It's way cheaper than cultured cells, plus all the clinics that do cultured cells are closed right now anyways because of Covid. Do a little research on intra-osseous PRP and bone marrow concentrate, the studies by Philippe Hernigou and Mikel Sanchez are pretty impressive. And yes there is evidence that bone injection can improve cartilage repair, so for a small lesion like that it might take care of both

I've read about ESWT and it sounds like it works well for bone but is pretty rough on cartilage, just too much energy. I've done a little research on bone stimulators that use electromagnetic energy to accelerate bone healing. They're commonly used to accelerate healing following spinal fusion. I don't have the studies on hand right this second but maybe I'll post some links later.
« Last Edit: December 09, 2020, 11:50:45 AM by db1984 »
2016: Patellofemoral OA, Lumbar DDD
2017: Regenexx-C both knees and lumbar spine
2018: 2nd Regenexx-C treatment
2020: Left knee arthroscopy, intra-osseous plus intra-articular PRP, cartilage ultrasound stimulation
2021: Got some new cartilage on my MRI!

Offline silver_maple

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Re: Where to get cultured stem cell procedure?
« Reply #48 on: January 31, 2021, 10:08:56 PM »
While this thread veered to electrical stimulation and other non-stem cell methods I wanted to return to the subject of stem cells.

Went through the entire 26 pages of the now closed 2008-2012 Regenexx thread. Recommended reading for new members of the past 2-3 years. Stem cells for knees were new then, PRP was new - there was unbelievable optimism among most posters that stem cells work and we are finally about to vanquish arthritis for good. Some thought than if not in 2010, then surely within the next 10 years. The odd poster with a dissenting opinion was labeled a troll.

Well, 10 years have rolled by. We don't appear to have moved forward much. The FDA has cracked down on cultured cells, the FDA also cracked down on SVF. BMAC is still allowed but stem cell concentration is woefully low and at least one study has come out equating BMAC to the low efficacy PRP https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029538/. The Lipogems procedure is still out there but is often maligned as a fat graft.

Even Regenexx-C, the Cayman Islands cultured procedure, is now thought not to be that much potent with Regenexx docs themselves recommending multiple Regenexx-SD instead (which are effectively BMAC=PRP). After the ~ 2010 facedown with the FDA, if Regenexx felt strongly about cultured, why didn't the company do a proper multi-phase trial and re-launch in the US?

The Teknon clinic in Barcelona has one study, likely with some bias, https://pubmed.ncbi.nlm.nih.gov/23680930/, that shows changes in cartilage quality, which they try to stretch as "regeneration" even though there is no evidence of cartilage volume changes. On the basis of this study high priced, low volume treatments are offered. My understanding is the Spanish medical authority approves each procedure on a one-off basis; cultured procedures are not available in the EU on a regular basis.

Some dose escalation cultured trials are still taking place. Korea has shown some efficacy with 100m cells, seemingly the floor for some effect; not sure if cultured are clinically available in Korea. I believe I saw a trial with Mayo testing up to 300m cells.

The original poster on this thread, Grove, was very gung-ho about cultured but he's gone silent after two posts and we don't know if he tried anything.

On the drug front, Invossa was beset by scandal although U.S. trials have now resumed. Sprifermin I don't follow closely but initial enthusiasm appears to have fizzled; I think they are still plodding along with trials.

So gloom has fallen over me, as a non-surgery hopeful. Conversations with several posters (Dave33, RGB) for patellofemoral joint issues indicate that after they wasted years on injections and other non-surgical approaches they finally found salvation in PFJR.

Is there anyone who can point to something verifiably hopeful on the stem cell front??
2019 - Chondromalacia patella gr 1-2, both knees; early bilateral tibio-femoral arthritis; 5mm focal chondral lesion (LK); degenerate meniscus tear (RK)
2020 - PRP x3 in RK
2021 - PRP x3 in RK, PRP x1 in LK

Offline db1984

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Re: Where to get cultured stem cell procedure?
« Reply #49 on: February 06, 2021, 10:50:25 AM »
silver_maple,

I understand your frustration. Sorry to steer the topic off cultured cells in my more recent posts... But since I seem to be the only person here who has tried it recently (and is actually reporting their experience) this thread has steered into other aspects of my knee strategy. No problem getting back on topic.

I understand that the discussion and excitement around Regenexx-C really peaked 10-12 years ago, and I think a lot of that has to do with the fact that it was available in the US and a lot cheaper back then. Back when Regenexx-C was available in the US it cost less than $10k, maybe even as low as $7k or $8k. Basically the same price as a same day BMAC procedure. Now in Grand Cayman it costs $19.5k, plus all the travel expenses making two separate trips to the island, and prices easily approach $25k to $30k. With the logistical and cost hurdles there are just a lot less people doing it now. Think about the number of people suffering from OA and cartilage injuries vs the number getting cultured MSC injections. We're talking about a tiny fraction of the patient population here. There are probably thousands of patients getting surgery for every one patient getting Regenexx-C. Just looking at those numbers it's not hard to see why we don't hear from many people who are trying this. And the ones that do likely aren't even on these forums. That being said, I have to disagree with the statement that Regenexx-SD is just as good as Regenexx-C, despite what the docs are saying. My suspicion is that they're making that recommendation from a a pragmatic perspective, ie. the SD procedure works well enough in patients when used properly, without all the difficulties of accessing cultured cells. If you read Dr. Centeno's blog though, where he gives occasional reports on patient results, pretty much all the Regenexx patients who had any significant cartilage repair got the cultured cells, which as far as I can tell is true after spending the last few years digging through most of his blog archives.

As far as cultured cells being the "final solution" for OA, clearly they aren't the magical silver bullet everybody is looking for, but it's still a VERY powerful tool to fight arthritis. As a simple joint injection it's better than anything else you're going to find. If you're talking about real structural regeneration cultured cells seem to have the biggest impact on the subchondral bone. This isn't trivial by the way, a lot of the recent research is pointing to subchondral bone as one of the main drivers of arthritis progression. I don't think the "cartilage quality" improvements seen in the Teknon studies are just smoke and mirrors. If you're getting big improvements in subchondral bone it seems very likely to me that the cartilage is benefitting as well. Bone-cartilage crosstalk is well documented. I've also spent many hours staring at my own before vs after knee MRI's and there is clearly an improvement in the cartilage after cultured cell injection, although it's not "brand new" again.

As far as BMAC and PRP are concerned the biggest advancement that's been made recently is understanding the importance of injecting the subchondral bone. If you read the Philippe Hernigou and Mikel Sanchez studies it's pretty clear this is a game changer. From what I've been reading the doctors in this space (especially Regenexx) are getting the memo and making that part of their standard practice, instead of just using it once in a while in "select patients" like they were before. Over the next few years as subchondral bone injection becomes more common I think the PRP and BMAC naysayers will start changing their tune. I definitely have. There's also some indication that this improves cartilage repair... The Hernigou studies noted cartilage improvements in the knees that received bone injection.

You mentioned dose escalation studies using 100 million cells and beyond. I don't think this is a simple issue of just dumping more and more cells into the knee until regeneration starts happening. The gene expression and differentiation of those cells to chondrocytes is a huge factor. 10 million highly chondrogenic MSCs is probably going to have a lot more effect than 100 million weakly chondrogenic MSCs. I think there's a lot of room for improvement here, as the approach so far seems to be to inject the cells and "hope for the best", without rehab programs designed to directly stimulate cartilage growth. Most doctors using MSCs are still approaching knee rehab from a a very old school perspective of focusing on improving the patient's function through muscle strengthening, mobility, posture, stability, etc. This approach certainly has it's place, but does very little to stimulate those cells to produce cartilage. This is why I'm so gung ho about ultrasound stimulation of cartilage. There's a lot of research (some of it over 20 years old) that ultrasound enhances the gene expression of both chondrocytes and MSCs and improves cartilage repair. And it does this without causing any damaging shearing or compressive forces to cartilage that's already been injured. There have also been a few animal studies published in the last few years demonstrating improved cartilage repair using ultrasound to stimulate MSCs after injection.

As far as why Regenexx didn't go the clinical trial FDA pathway to getting approval in the US, they actually did license Regenexx-C to a biotech company called Biorestorative Therapies which was running phase 2 FDA trials, mainly for the application of low back disc bulges. Unfortunately they filed for bankruptcy, but I read another company bought them and have picked up the ball. Regenexx also announced a couple months ago that they're opening a second cultured cell facility on Hainan island in China. Because of Covid all of the overseas clinics have been shutdown for the last year but they should start reopening in a few months as people get vaccinated.

So I disagree that the non-surgical stem cell route is dead. If you're looking for hope read the Philippe Hernigou studies on intra-osseous BMAC injection, as well as the studies on intra-osseous PRP by Mikel Sanchez and others. Also read some of the studies on using ultrasound to enhance chondrogenesis. I think part of the reason outcomes have been lackluster is because doctors are still figuring out how to use this stuff effectively. Real success is going to require a comprehensive approach targeting both cartilage and bone, stimulating cells to produce cartilage, etc. Simply dumping more and more cells into the knee isn't going to cut it, which I think is pretty clear at this point.

Okay I'm done with this rant. Your frustration is justified but don't give up hope. Progress is still being made on the non-surgical front.
« Last Edit: February 08, 2021, 12:42:30 PM by db1984 »
2016: Patellofemoral OA, Lumbar DDD
2017: Regenexx-C both knees and lumbar spine
2018: 2nd Regenexx-C treatment
2020: Left knee arthroscopy, intra-osseous plus intra-articular PRP, cartilage ultrasound stimulation
2021: Got some new cartilage on my MRI!















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