Looking to treat severe knee medial compartment OA

[ubercool]

You'd need to ask a surgeon

I thought that after 12 years of moderating this forum you would know everything!

[vickster]

I've not been an admin for 12 years, just had a rubbish knee for that long.
I'm not a medic, you need an expert opinion on such things

[silver_maple]

Ubercool, sorry for taking me some time to get back to this lively thread - I have been monitoring posts but too many balls in the air to respond properly.

From your x-rays the left knee appears to be bone-on-bone medially and this is the likely source of your pain. Can't detect the osteophytes but once you get bone-on-bone osteophytes are likely to develop.

I understand your hesitance to go for TKR. On the other hand, you have entered the ideal age range for TKR 70-80. Did you manage to consult with Dr. Hanson?

Your question on the ideal source of stems for cartilage regeneration is difficult to answer. There is the lab view and then there is what's available bedside.

The following paper is a good overview of biomolecular approaches to regenerating cartilage and is a downer. But this is the correct serious approach to biotech. Eight years old but to the best of my knowledge, there hasn't been a quantum leap forward since. Corresponding author is the doyen in the MSC space Arnold Caplan. https://pubmed.ncbi.nlm.nih.gov/24749845/

A more recent comparison right along the lines of your inquiry:
The efficacy of different sources of mesenchymal stem cells for the treatment of knee osteoarthritis https://pubmed.ncbi.nlm.nih.gov/31309317/

In practice you'd be limited to BM-MSC or ASC. If you read the above two papers you'll know pure MSCs is not the holy grail. Dr. Centeno has been trying that in the Cayman Islands for 10+ yrs with no great success. In the US and EU adding inductive morphogens like FGF-2 or BMP-7 is not allowed outside of clinical trials.

Nevertheless, quantity of stems matter not so much for their potential to engraft and differentiate but for their releasate (for cell-free approaches with exosomes we can talk another time). As far as I know Dr. Centeno sticks to BM-MSC only, likely in the concentrate form BMAC. Even concentrated I think BMAC has much fewer stems than ASC. Check with Dr. Centeno for the latest technique, I recall him saying he drills at multiple spots (5-10) in the iliac crest in order to improve yield. And stems in BM decline precipitously with age, I think anyone over 50 should pass. And do you want to be bone-drilled multiple times?

The main problem with many stem studies for KOA is that they focus on patient reported qualitative outcomes. Examples galore. Cynically one could think these are marketing materials behind a thin scientific veneer. Many providers like including "regenerative" in their business name yet evidence for regeneration is slim.

One of the few exceptions is this Croatian study of Lipogems with 24-mo follow up. It used an advanced quantitative MRI technique to analyze cartilage composition and found increased glycosaminoglycans content in the matrix. Study participants were similar to you: mean age 69, with Kellgren-Lawrence III or IV. https://pubmed.ncbi.nlm.nih.gov/31861180/

Dr. Hanson will likely recommend TKR and advise against wasting time and money on unproven, low-efficiency stem treatments. At that point you'll have a decision to make.

Best.

[ubercool]

Thanks silver_maple, unfortunately Dr. Chad Hanson is a busy man and I couldn't get an appointment until 3/31, so basically April.

Reading about all the potential TKA problems that can crop up ("Finding help for post knee replacement pain" https://www.caringmedical.com/prolotherapy-news/pain-knee-replacement/) and noting that TKA revision surgery costs $74,000 on average (https://journals.lww.com/clinorthop/Fulltext/2006/05000/The_Increasing_Financial_Burden_of_Knee_Revision.34.aspx), I'm firmly resolved to try anything before subjecting myself to an invasive operation.

Based on MDAL and psny's recommendations, I've decided to focus on an SVF (Stromal Vascular Fraction) treatment that uses enzymes to separate stem cells from adipose tissue. And psny says PRP is an essential anti-inflammatory and recommends the Emcyte Pure PRP II separation system, which is "one of the best in terms of platelet concentrations."

I'm leaning toward Dr. Harry Adelson because I can drive to Park City in six hours. I understand he does SVF.

Thanks for the Caplan paper. I saw a video in which Caplan spoke highly of Dr. Carlo Tremolada. And I also watched the video you posted in which Tremolada operates with Dr. Slynarski in Poland. Did you ever decide to see Slynarski?

[silver_maple]

Hi ubercool,

I exchanged e-mails with Dr. Slynarski, he was very prompt in replying. Dr. Slynarski is one of Dr. Tremolada's early "disciples", if I can say so. Curiously, he no longer lists Lipogems on his website but he did confirm to me he still does Lipogems. Dr. Slynarski is on my short list of providers. Like you, however, I did not feel all comfortable flying halfway around the world for a procedure that is low surgical skill and quite standardized, plus Covid made things even more of a hassle. I am prepared to try this closer to home and frankly was surprised when a surgeon in the Detroit area, who also does Lipogems, advised me against it this past summer. I specifically asked him about the downside, he said there was none but also no upside, i.e. waste of money.

My current plan is to do a simple PRP refresh in the coming months. My doc recommends a PRP maintenance shot annually. Doesn't do much for regeneration but promotes homeostasis. At this stage my knees tilt slightly in the catabolic direction given OA is a progressive degenerative disease. The process is slow, I probably have ~15 years until TKR but don't want to just sit and wait like a patsy.

Please double-check if Dr. Adelson still does SVF. He used to for sure but the FDA may have shut him down. Enzymatic digestion may not be seen as "minimal manipulation", the regulatory exemption that allows MFAT to be offered.

[ubercool]

Hi silver_maple:

There seems to be a few doctors who offered Lipogems and then stopped offering/promoting it. Purita comes to mind.

Dr. Adelson now charges $200 for a telephone consultation but I will ask his assistant about SVF before we get on a call.

[ubercool]

OK, just got off the phone with Dr. Harry Adelson. He confirmed that he still does SVF and offers that in combination with BMAC, Organicell "Nano-Particles derived from amniotic fluid" and VSEL for what amounts to double the fee quoted by Regenexx, albeit without many of the above esoteric treatments.

I could strip out the BMAC, Organicell, and VSEL to bring the cost down to a more palatable level, leaving me with just the SVF treatment. I had never heard of Organicell but found this press release dated last year:

https://www.businesswire.com/news/home/ ... oarthritis

And more about VSELs here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430762/

What would you do?

[ubercool]

Adelson's assistant emailed me to tell me that Docere only offers the "kitchen sink" so it's $21,000 or nothing.

[silver_maple]

Ouch, that's rather steep, ubercool. I am inclined to think this is a money grab. Had not heard of Zofin itself, appears to still be in the trial phase. Will explore further over the weekend. The cell-free concept itself is not new, already available in Germany (e.g. Anova IRM). Have reservations SVF can legally be offered, ideally you'd cross-check with a Utah regulator. In any case, there should not be legal risk to you as a potential patient.

I consider SVF and MFAT to be roughly equivalent. Many SVF vs MFAT studies give MFAT an edge but a good chunk of these studies have been authored by Dr Tremolada or researchers close to him. One example: https://pubmed.ncbi.nlm.nih.gov/30255987/. I have seen at least one study that gives SVF the edge.

The main issue is safety. Both SVF and MFAT appear safe, any complications such as swelling are transient, and any issues at the harvest site tend to be minor and treatable. Importantly, there is no evidence of neoplastic formations - in the joint or systemically. This double-blind randomized trial (close to the gold standard) attests to SVF's safety https://pubmed.ncbi.nlm.nih.gov/30109404/. There are many more.

Opinion is divided on effectiveness in terms of regeneration. Improvements to pain and stiffness of various duration are commonly seen but these metrics are patient reported and likely suffer from upward bias.

I understand your reluctance to undergo invasive surgery. On the other hand you are TKR-eligible in terms of symptoms and age. At least in this forum you have not shown much interest to explore the TKR alternative. There is probably a section on TKR with post-op experience, or you could start a new thread. There are certainly active members here who have had TKR, you may already have friends with TKR. Approx. 80% of TKR recipients are satisfied.

I'd say, tough it out until you see Dr Hanson in late March and hear the other side. You could call into his office every 3-4 days and check for cancellations, maybe you could move up the appointment. Ask him about the revision risk if you do TKR now, longevity runs in the family, and you intend to be physically active. Tell him about the biologics option you are considering, expect him to be skeptical. Confirm there is no downside risk. If after that meeting you still intend to pursue stems, look into MFAT. Depending on how responsive you are you could get 1-3 years of pain relief. I view the MFAT procedure as low surgical risk, highly standardized, so no need to travel overseas. A name you yourself raised previously - Dr Joanne Halbrecht in Idaho, may be worth checking in with.

Best.

[ubercool]

silver_maple thanks for the feedback. Think about it, in June 2013, ashok_guru mentioned that Dr. Adelson charged $1,400 for injecting two knees. How things have changed!

The majority of research I could find for Zofin was for a Covid-19 treatment but this article in Future Medicine has more information:

Zofin is an acellular biologic therapeutic derived from human amniotic fluid. It is manufactured to retain naturally occurring miRNAs, without the addition or combination of any other substance or diluent. This product contains over 300 growth factors, cytokines and chemokines as well as other extracellular vesicles/nanoparticles derived from amniotic stem and epithelial cells. The product contains a mean concentration of 5.24 xc3x97 10****11****particles/ml with a mean mode size of 125.2 nm. Surface marker analysis confirmed the presence of exosome associated proteins CD63, CD81 and CD9 in addition to high expression of CD133. The completed sequencing revealed 102 commonly expressed miRNA (with a 100-copy expression minimum). Bioinformatics analysis linked 63 miRNAs to 1216 RNA targets. Major players in the pro-inflammatory cytokine cascade found to be targeted by miRNA discovered in Organicell's product include TNF, IL-6 and IL-8. Additionally, a broader array of pro-inflammatory cytokines is also targeted by the collection of miRNA such as FGF2, IFN-xcexb21, IGF-1, IL-36a, IL-37, TGF-xcexb22, VEGFA, CCL8 and CXCL12. It has been suggested in published research that inhibition or suppression of this pro-inflammatory cytokine cascade may reduce the severity of symptoms associated with elevated immune response.

Source: https://www.futuremedicine.com/doi/10.2 ... -2021-0065

So, if it's a Phase I/II randomized, double blind, placebo trial how does Dr. Adelson add it to my treatment as a routine procedure?

While I would like to see Dr. Halbrecht for an MFAT treatment, I have to address my issues now. I need more mobility and freedom from pain. I will, however, agree to hold off on Regenexx until after I see Dr. Hanson.

The Regenexx advantage is that I can have both lumbar spine and knee injections done at the same time by Dr. Centeno himself, at a reasonable cost. I'm pretty sure Dr. Halbrecht would charge me almost as much as Regenexx just to inject one knee. I know Dr. Tremolada would have excluding travel expenses.

And given that I will post my experiences here, forum members will benefit from a first-hand experience with adequate post-op follow up. The few case studies from a variety of practitioners I found here are all spotty at best, lacking long-term feedback about the effectiveness of their procedure.

Thanks again.

[ubercool]

DOCTOR UPDATE

So, I have now done the rounds and I am updating this post. I'm still short one provider, Dr. Chad Hanson, but that appointment is not until March 31, so I will add his input then. To recap, here's who I have seen/spoken to since my adventure began in September:

Dr. Chris Centeno/Regenexx Centeno-Schultz Clinic
I started my journey in Broomfield, Colo. where I was examined by Dr. Centeno himself. I have been following his blog posts since 2015 and I know the man knows of which he speaks. I also know that Regenexx has a data-based, scientific approach to stem-cell therapy, which made this a must visit. Dr. Centeno recommended a Regenexx SD left knee single joint injection using their tried-and-true BMAC/PRP extraction and injection procedure. Cost including injecting my bad back was north of $10K.

Dr. Carlo Tremolada/LIPOGEMS inventor/Image Regenerative Clinic, Milan
Dr. Tremolada thought I would be an excellent candidate for his MFAT procedure since I was a grade 2 on the lateral side and a grade 3 on the medial side. He guessed I had OA in both knees and offered to inject both for under $10K with booster shots needed after 2-3 years, since studies show a response rate of only 45% after a single intra-articular injection of autologous MFAT. His opinion is that a Lipogems treatment would help me stave off a TKR for 3-5 years, but like an expectant mother, results would only show up after nine months. When you add travel costs, getting to Milan would boost the total to nearly $15,000, plus the risk of a negative reaction, this option became less attractive despite Dr. Tremolada's obvious pedigree.

Dr. Joseph Purita/The Institute of Regenerative Medicine, Boca Raton
Purita believes stem-cell therapy would be beneficial for 2-3 years. His treatment regimen requires an initial visit to Florida for BMAC harvesting and injection. It would also require two more trips to Boca Raton for PRP booster shots at 3-6 week intervals. Cost would be around $8,000 for both knees. Once again, travel would be the inhibiting factor here, with three trips required at about $1,500+ for each trip. If I lived in Miami, Purita would be a no-brainer.

Dr. Harry Adelson/Docere Clinic, Park City, Utah
Despite Adelson's rather friendly demeanor, his office manager, Linda Morgan, said Docere only offers the "kitchen sink" for $21,000 but if I wanted a bargain-basement treatment (my words not hers ), check out Dr. Crispino Santos at Regenerative Stemcell Institute in Las Vegas. I searched this forum for Dr. Santos and found no results. Googling the doctor, I found a rating of two stars based on 28 reviews on Healthgrades. While I appreciated the intent and spirit behind the recommendation, I decided to pass. BTW, the "kitchen sink" does not include PRP Adelson no longer offers that.

Dr. Carlos Guerrero/Stemwell Medicina Regenerativa, Bogota, Colombia
Dr. Guerrero was recommended to me by my brother, who lives in the Caribbean, a stones throw away from Colombia. Dr. Guerrero is an orthopedic surgeon whose Stemwell clinic offers both BMAC and allogenic umbilical cord injections for the princely sum of $4,100, including ascorbic acid (vitamin C), anesthesia, physiotherapist, and even testosterone cream. You can quickly see why Colombia has become the medical tourism capital of South and Central America. Unfortunately, Dr. Guerrero is a firm believer in his own orthopedic skills, and was dismissive of needing fluoroscopic needle guidance (Centeno: these machines costs $250,000, so not many doctors can afford them). And, of course, the treatment requires at least a five-day but optimally a 10-day visit to Bogota, so your stem cells can be adequately cultured.

Dr. Leslie Vidal/Steadman Clinic, Vail, Colo.
If you live anywhere near Vail, don't hesitate to sign up for your free BMAC knee stem-cell therapy at Steadman Clinic for a double-blind OA study. All you have to do is pass their screen; potentially get dizziness, headache, diarrhea, and stomach pain from taking Losartan and Fisetin (or luck out and get the placebo sugar pills); make eight trips to the Vail clinic; plus record every single thing you feel, and you're in! Wish I lived in Vail!

Dr. Kevin Stone/The Stone Clinic, San Francisco
Dr. Stone gave it to me straight today. My bone-on-bone situation could be repaired by patching the defect with an artificial meniscus but he felt that a partial knee replacement was a sounder approach. Listening to my worries of lingering pain and possible risk of infection, he said that 98% of his PKR patients had no pain and infection risk was very rare. Dr. Stone uses a knee surgery robot, I didn't ask him which one, but it was either the The Mako by Stryker (Kalamazoo, Mich.), Navio/BlueBelt from Smith & Nephew (Andover, Mass.) or ROSA from Zimmer Biomet (Warsaw, Ind.). Amazingly, the arthroscopic PKR procedure lasts just one hour thanks to Dr. Robot. Of course, The Stone Clinic is an out-of-network provider, so the self-pay damage is $21,000. However, they'll be happy to submit a claim for the ambulatory surgery center.

Dr. Josh Goodwin/Regenexx, Las Vegas
Each one of the above options requires travel costing upward of $3,000, if not double that. So, I thinks to meself, "self, why not avoid all the hassle and go see a good local doc." Today, I met Dr. Josh Goodwin who represents the Regenexx brand in Las Vegas. I told him about my extensive research in the matter and my conversation with Tremolada about MFAT. He said that adipose stem-cell treatment had its place and that a doctor at Regenexx HQs practiced it when appropriate like for multi-site application of stem cells when a BMAC extraction simply does not deliver enough. Goodwin was also the first doctor to bring up intraosseous injections (injections in the subchondral bone), favored by db1984, to improve long-term results. Since no travel is required, this is, by far, the best option.

I hope all you lurkers are enjoying my generous information. Given that this thread has attracted 1,120 views but just four commenters, there must be a some interest in the topic. Please like this post, thank you!

[Elce]

Hi Ubercol, William Bugbee does fresh osteochondral allograft reconstruction of the knee.

[vickster]

Aren't allograft and indeed autograft transplants usually reserved for patching up single focal defects in younger patients (with good alignment and intact meniscus) rather than widespread cartilage loss /wear and tear in older patients? The OP is 70. He's also trying to avoid invasive surgeries, focusing on injections

[silver_maple]

Ubercool, thanks for the detailed update.

Like Lipogems, Regenexx is quite standardized. Not sure of all the business details but stands to reason there is branding and maybe franchising involved. To be able to say/offer Regenexx other docs adhere to specs Dr Centeno has developed for all Regenexx flavours such as Regenexx SD, for example. My point is similar to that I've made for Lipogems (itself trademarked) - variability of outcome as a function of doctor skill is likely low. Far greater determinants are initial condition and maybe age. So going local looks fine with me.

Harvesting is more invasive with BMAC and you haven't mentioned if it's going to be one pluck from the iliac crest or multiple. Are bones more brittle at 70 and could multiple punctures of the iliac crest be more destructive than on someone aged 30? I don't have ready answers.

Yes, there is great interest in this thread as the stems topic had been quiet for a long time. I don't think we've hit the holy grail yet but research keeps crawling along. Somewhat surprisingly S Korea is one of the leaders, I am monitoring a couple of US clinical trials by S Korean firms but it's still early stages. You've done your detailed homework, looks like you will wait to see Dr Hanson before making the final call. Please keep us posted!

Best.

[ubercool]

Hi silver_maple, Dr. Goodwin emailed me himself, now that's what I call service.

Here's his answer:

We typically aspirate from 3 sites on each side of the iliac crest. So 3 on the right and 3 on the left. It is one skin puncture site and 3 sites at the bone.

There is no concern for weakening of the bone. We have performed bone marrow aspirations on patients in their 90s. We have had patients with diagnosed osteoporosis without issues. There are very large studies looking at complications from bone marrow aspiration and is a very safe procedure. Most common complication was bleeding. Which is why we don't want people on blood thinners. Weakening of the bone was not seen in those studies or in our registry data regarding complications.

So it is not typically something we tend to worry about. Obviously with everyone, we take our time with the procedure and try to minimize trauma to any area we treat or harvest from.

Let me know what you find out from those So. Korean studies, curious to know.

Harvesting is more invasive with BMAC and you haven't mentioned if it's going to be one pluck from the iliac crest or multiple. Are bones more brittle at 70 and could multiple punctures of the iliac crest be more destructive than on someone aged 30? I don't have ready answers.

Yes, there is great interest in this thread as the stems topic had been quiet for a long time. I don't think we've hit the holy grail yet but research keeps crawling along. Somewhat surprisingly S Korea is one of the leaders, I am monitoring a couple of US clinical trials by S Korean firms but it's still early stages. You've done your detailed homework, looks like you will wait to see Dr Hanson before making the final call. Please keep us posted!

Best.