One of the most common claims made by unproven, for-profit stem cell clinics is that the stem cells they are selling can help knee arthritis and associated pain, but what is the evidence to back this up?
There are many problems with the claims of stem cells for arthritis being made across the U.S. In quite a few cases what is being sold isn’t even real stem cells. It often is an amniotic extract, which probably isn’t from actual stem cells anyway and is “dead.” But what about cases where real, live stem cells are being injected every day for knees arthritis and other kinds of joint problems?
The CIRM Blog recently covered the issue of stem cells for knee arthritis in large part inspired by a new comprehensive study that sheds major doubt on this approach. Some of the main take-homes from the study were nicely summarized by Kevin McCormack of CIRM:
“In a study presented at the Annual Meeting of the American Academy of Orthopaedic Surgeons, researchers contacted 317 clinics in the US that directly market stem cell therapies to consumers. They asked the clinics for information on the cost of the procedure and their success rate.
- Only 65 clinics responded
- Lowest price was $1,150
- Highest price was $12,000,
- Average price of $5,156.
Only 36 clinics responded with information about success rates.
- 10 claimed between 90 and 100 percent success
- 15 claimed 80 to 90 percent success
- 10 claimed 70 to 80 percent
- One said just 55 percent.
None offered any evidence based on a clinical trial that supported those claims, and there was no connection between how much they charged and how successful they claimed to be.”
Put it together and it paints a negative overall picture of the clinics in this sphere. Patients are paying around $5K for a kind of stem cell treatment where clinics are largely claiming 70-100% success, but yet have little or no evidence to back it up. The average cost data here fit well with the numbers in a poll I did about 6 months ago on this blog of what patients say they paid for stem cell therapies more generally.
McCormack has quotes both from the lead authors, Nicolas Piuzzi and George Muschler, of the study entitled, “The Stem-Cell Market for Treatment of Knee Osteoarthritis: A Patient Perspective“, which is published in Journal of Knee Surgery with some big picture perspectives and thoughts on the meaning of their work.
Basically, there’s a disconnect between the state of the clinical science in this area and what is being widely marketed for profit. I’m not aware of massive patient side effects in this area so safety, while not assured by any means, is not perhaps the biggest issue. However, there is minimal evidence of efficacy from properly controlled studies. For instance, the authors of this study suggest potential benefit of bone marrow stem cells for knee arthritis, but although it did have a control group, it wasn’t blinded and was underpowered. Here’s a more recent, blinded study arguing for some moderate benefit, but it was underpowered as well and no benefit was seen after 12 months.
The bottom line in my view is that stem cells for arthritis from clinics directly marketing to consumers is most often going to be a big waste of money for patients. This is not to say that there’s no hope of stem cells for arthritis or specifically for knee arthritis, but caution is in order right now on this front. There needs to be more rigorous data on efficacy. I hope in the future we get that data as a field so we can have better clarity here. You can see some past posts including knee arthritis here and it’s apparent that for up to 8 years or more this issue has been percolating.
Hi Paul,
I agree that more data will help us determine which patients are the best candidates and what the treatment response rates are for each individual indication, which indications require only PRP, which ones BMAC, which ones both, etc. The thing I see missing from your discussion is a summary of the excellent clinical research conducted by Philippe Hernigou at Univ of Paris since 1990. He’s treated over 4500 patients for a variety of indications including osteoarthritis, rotator cuff tears, non-healing infected fractures, and avascular necrosis of the hip. Most of his clinical studies are controlled prospective studies often with follow up periods averaging at least 8 years. I would like to invite you to join us at the Interventional Orthopedic Foundation meeting this coming February or TOBI this summer. It is important to separate the ScamCell Clinics from the group of well trained, ethical clinicians trying to advance this field and help their patients so that the FDA does not bring a hammer down on everyone. This would be a disservice to the many patients that are left to help such as my patient crying in my office after being turned down for joint replacement because she was “too old”. All of the treatments I was performing were based on Hernigou’s research which had excellent data behind it.
Regards,
David Smith MD
Columbia College of Physicians and Surgeons 1991
Anesthesia Residency Cleveland Clinic Foundation 1995
Regional Anesthesia Fellowship Virginia Mason Clinic 1996
Interventional Pain Physician Kingston, Ontario
Thank you for the information .I have had knee pain after my car accident 2 years ago and I have been to almost every doctor. My current doctors are pain management doctors in rockland county ny who I started to see 4 months ago. He has given me medications and treatments but also some physical exercises, which have help me alot in these 4 months.I just hope the pain could completely go away.
Can anyone recommend me a better way of treating my pain?
Any thoughts on actual marrow obtained stem cell treatments for fresh meniscal tears? I’m sure their is a paucity of reliable studies, but does this have a better chance of success in your opinion/s?
I find it odd that such negative reviews over autologous stem cell therapy for knee pain is reported at an annual meeting of Orthopaedic SURGEONS. Stem cell therapy is medical advancement. Sure, stem cell treatment may not be successful for 100% of patients, but what treatment is?? PubMed has several Randomized Control Trials listed that suggest that stem cell therapy works for many, many people. Don’t worry surgeons, the stem cell treatment will not likely bite into your surgical pockets, but come on guys, shouldn’t it be the parient’s health and quality of life that comes first? Also, while I’m thinking about it, I have read that there is a slightly elevated risk for heart attack for patients who’ve undergone total knee replacement surgery. How ’bout we keep things transparent. Thank you.
Randomized control trials do not at all “suggest that stem cell therapy works for many, many people.” Doing any experiment or trial is a way of gaining data to determine whether the hypothesis behind the experiment is true or not.
Randomized control trials in fact indicate that the jury is out.
MO! NO! You may have not given yourself enough time to regenerate and heal! I have had PRP injections in both knees 4 years ago and my Dr. told me that they would last for 4 years….however I HAD to stay off my knees or any heavy lifting for 6 weeks. I am no weight trainer, but MAN that is literally TONS of weight you are putting on your knees and body. I have also heard the B.S. line…you are able to go back and do 100%….DON’T fall for that one brother….EVER. I have stage 2 tears in my knees and cannot walk through a grocery store…waiting for my PRP therapy…in the meantime may I suggest seeking a Massage Therapy EXPERT who can help you….
Perhaps it is simply that after a treatment or two the patient does NOT return, therefore there is NO follow up to determine wether the effects were positive or negative. I have a friend who paid DEARLY in the early 2000’s for 3 treatments on each knee and has had no problems since. She is now looking into having the same done for her HIPS as she is now turning 80 and does not want hip replacement! That sounds good to me!
I am going to speak for myself , I did 2 stem cell and over 12 PRP injection on both of my knees in the past year, it didn’t help me at all it made my knees worse, I lift weight and I compete at powerlifting and strongman , I feel my knees were much better before all this stem cell and prp, I have grade 3 cartilage lost in my knees, I was promised to be back to all my actvities 100% , after I finished my stem cell treatment and paid 8700 out of pocket the stem cell Dr, or therapist I don’t know what to call him said to me few months later not to squat more than 50 pounds for the rest of my life , I looked at him and said , “ you told me I should be back to my activities 100% and I used to squat in the 600s why would I do stem cell to be at 50 pounds only !!! “ it’s waste of money, my knees are worse there is no benefits to it , I did my first stem cell July 13th 2017, followed by another stem cell September 14th 2017, after after that I did PRP injection every two weeks to boost the cell for faster recovery and better results , nothing helped … these past few weeks I ordered Pentason from race horse med , and I’ve been shooting my own knees and I can tell it helped me more than stem cell and prp , a bottle of pentason cost 49 bucks and a will last me few months , better than stems cell 8700 and prp 150 per injection , this is just my personal opinion I’m not a dr or anything I’m just a weight lifter. Now I’m considering cartilage shaving surgery not sure yet .
Can stem cell be used for torn meniscus muscle?
I’m an XYZ patient and have been treated by Dr. XYZ as well as several other doctors in his practice. I developed early OA in my knees at a relatively young age (early 30’s) and was determined to give stem cells a shot. I had injections of culture expanded stem cells in XYZ. The treatments have made a huge difference for me in terms of quality of life, and I also have before and after MRI’s of my knees showing the structural improvements that followed the stem cell injections. Note that I had the same image sequences taken on the exact same scanner, so the comparison is legit. Before that I tried one of the “same day” stem cell treatments in the US and it did very little to improve my condition. For me, the experience of receiving same day vs cultured stem cells was like night and day!
I have spent the last 2 years reading the published literature on stem cell treatments for OA. If the only thing you care about are randomized controlled trials, then here is what has been published, at least to my knowledge:
https://journals.lww.com/transplantjournal/Fulltext/2015/08000/Treatment_of_Knee_Osteoarthritis_With_Allogeneic.27.aspx
https://journals.lww.com/jbjsjournal/Abstract/2014/01150/Adult_Human_Mesenchymal_Stem_Cells_Delivered_via.2.aspx
https://www.sciencedirect.com/science/article/pii/S0749806313010736
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-0998-2
https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-017-1391-0
https://www.sciencedirect.com/science/article/pii/S1465324914000644
Note these are just randomized controlled trials for cultured bone marrow stem injections for knee OA. There are some for adipose stem cells but I haven’t included those. Also, there are many more case studies using the same type of treatment in which there wasn’t a placebo group, but the patients were tracked long term (up to 4 years) and their knees were analyzed by MRI… but again I didn’t include them in the list because they weren’t randomized controlled trials. That’s kind of a moot point though… does anybody seriously think the placebo effect will grow MRI confirmed cartilage in an arthritic knee?
i was very intruiged by the 100×10(6th) cultured cell results … in the USA, doing non-cultured stem cells is more/less a waste of time/money .. the cell count needs to be in that 90-100million marker to make-a-dent in knee OA
any update on the adipose stem cell studies you referenced above?
Hi TJF,
I’m not sure about the adipose studies, but I can comment on my own results with cultured bone marrow cells. It’s been about a year and a half since my first knee stem cell injections, it was about 20 million cells in each knee. I had a second smaller injection of about 4 million cells 7 months ago. Pain and function-wise my knees have significantly improved, but still have some issues. Structurally, while there was some cartilage healing, there hasn’t been major cartilage growth. MRI’s show improved cartilage signal on the T2 scans and a little thickening, but not much. The biggest change was the bone marrow lesions in my knees, which healed almost 100%. I’d say we definitely put a dent in it, but I think at some point I’ll opt for surgery for more significant cartilage growth. While the cell injections definitely have regenerative potential, I think there’s a ceiling to how much they can regenerate without surgery. The technique developed by Dr. Khay Yong Saw is most intriguing to me at the moment.
I think for non-cultured cells there’s good regenerative potential when combined with marrow stimulation and repeated injections. There are some doctors using this approach and getting decent cartilage growth.
Thanks,
Dane
Thank you for the healthy debate and all of the blog information. I clicked on this particular article because I’m hoping to find more information on osteo arthritis and stem cell effectiveness. However my issues are in my hands.
I can only find information on knee osteoarthritis in all the articles I’ve read.
Never anything on the painful painful hand osteoarthritis. If you’re able to direct me to any studies or information on regenerative medicine for the hands please let me know. Thank you. PS – Ihave to speak these entries and thus there maybe typos. That’s how much my hands hurt. And that’s how desperate patients are.
Hi Karla, it’s June 19, 2018. I read your entry here and hope you get this reply. I’m in Alberta, and I’ll make this short. I am prexently 63 yrs old, and I have both knee osteoarthritis and thumb osteoarthritis. MRI of July 2015 of knees, in short they’re bad, I’m bone on bone and was in a lot of pain. Arthroscopic surgery right knee March 2016, othopod surgeon wouldn’t even check it 2 wks postop and offered no help or advice. Had off loader brace made to help with pain. May 2016 had my own bone marrow (pelvic) used for stem cell treatment injected in both knees and thumbs, and prp (platelet rich plasma) injections (in short it helps boost stem cell treatment) treatments Nov/16 and Dec/17. Two full years and some degree of pain back, but oh so much better than before the treatment. It’s a subjective result, but that counts for a lot too! I have a nursing background and I won’t try something that doesn’t have medical credibility to it (however I know that desperate feeling of needing relief). I hope this post helps you in making some decisions for yourself. I know it hasn’t helped everyone. All the best, Gloria
It did miracles for my knees…I no longer need double knee replacements!!!
Can you go into more detail if more time . Thanks Ray
Dear Admin:
Often the best thing about your often highly biased blog is that it motivates readers like Richie and Douglas Atkins (terrific rebuttals!) to present more of the total picture of what has been reported in this exciting, and still emerging, field of biomedicine.
James at Asymmetrex
@Douglas Atkins
Here is another very interesting paper concerning osteonecrosis:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761591/
very interesting results:
“Hernigou and Beaujean3) have published clinical data on their experience. They treated 189 hips in 116 patients with autologous BMCs and had a follow-up of 5 to 10 years. Satisfactory results were achieved in the majority of patients according to improvement of the Harris hip score, radiographic assessment and refusal of THA. The prognosis was not only highly related to the stage of disease, but also to the progenitor cells transplanted.”
“In 2008, Hernigou et al.16) retrospectively analyzed 534 hips in 342 patients with ONFH treated with autologous BMC transplantation. The results were really encouraging. They showed that the volume of necrosis would decrease from 26 cm3 to 12 cm3 in 371 patients with an average follow-up of 12 years. There were only 94 patients who progressed to THA”
I think this review shows good data. Of course no double blinded and controlled study. But in my opinion it should be better to try this therapy instead of a big surgery with an unknown outcome.
All the best
Richie
@Douglas Atkins,
just take a look at this interesting article, too
https://www.regenexx.com/avascular-necrosis-treatment-without-surgery/
Thank you, Richie. I read this after clicking on your link. If I had some kind of osteonecrosis of the knee and other areas, I would, as a patient, make first an attempt at the far less invasive approaches to repairing the damage by way of expanded adult stem cells before moving on to something like knee replacement surgery or some of the other invasive procedure. I’d like to be given that choice at the very least. It’s pretty frightening what Dr. Centeno wrote about the use of Prednisone. I’ve met colleagues with asthma and severe allergies before who’ve been placed on that drug in times past. And while they say it works wonders for them, I’m not sure they know the long term consequences of having been placed on Prednisone even once. I certainly had no idea. And of course some MD’s dispense it like Halloween Candy. Same with Statins. What seems to be the most effective least invasive method of treating osteonecrosis: (expansion of cellular material to higher therapeutic levels for injection into the damaged bone) is naturally not legal in the United States. So once again, patients are being disenfranchised state side because the powers that be think they know so much more than the rest of us. Thanks again for the link, Richie. Best..
Doug
Centeno isn’t an orthopedic surgeon and knows nothing about it. He’s a marketing/business genius who got a 22 million dollar head start late in the game.
“If stem cells for arthritis really works, then large , double blinded and properly controlled studies should prove that”
A few things about this statement. You say the study above is weak scientifically. Yet, medically it does not appear to be that way. (Or else it likely would not have ever been published!) You are making your statement about scientific weakness regarding a clinical study as a non clinician. You are not a healthcare provider. You are not a Doctor. Additionally, Doctors, generally speaking, are clinicians and not scientists. They are practitioners. The practice of medicine is not a pure science. Large double-blinded placebo controlled multi center international clinical trials are as unbelievably expensive as they are lengthy; taking sometimes several to many years to complete. And then there exist the interpretation of those results or data. You can then probably add a few more years to that as well before something becomes the standard of care. That sort of data and the published papers they generate are generally not all that readable to the public. But the study that I just cited most definitely is. It is fairly straightforward and interesting as well. Others similar to it have been published from practitioners like Dr. Chris Centeno MD who also utilizes expanded or cultured stem cells.
Even those not trained in science and medicine, can draw their own populist conclusions from studying these kinds of fairly readable clinical trials. I and probably many others in a populist sense just do not see autologous stem cells as requiring the kinds of studies that you are referring to particularly when smaller, less expensive and less time consuming studies will likely suffice when taken as a whole. These as well as more thorough studies can take place all the while employing adult stem cells as the standard of care without having to wait decades for academics to render their analysis. Larger studies are generally the purview of those who can afford them like the big pharmaceutical companies. They are likely, for reasons of profit, not interested in sponsoring double blind multi center international clinical trials on that which they cannot patent.
Attorney Richard Jaffe has noted in one of his blog pieces that it is this very sort of burdensome and restrictive governance with reference to our own body parts which has prompted others to note that “if they had the regulatory environment back then as what exists today, bone marrow transplants might never have taken off.”
So for me regarding adult stem cells, the issue is,…why use a sledge hammer when a feather duster will do? Elitists might not see it this way. And I do believe that we need their opinion. I just don’t think expert opinion ought to have the last word. Where health care is concerned, it is far too important an enterprise to leave just to the experts.
Honestly! I think the title of this blog piece “Bigger picture study casts big doubts on stem cells for knee arthritis today” reflects a confirmation bias on the part of the editor against the practice of regenerative medicine more than anything else. Without too much effort I was able to find the following …
https://www.ncbi.nlm.nih.gov/pubmed/?term=Intra-articular+injection+of+expanded+autologous+bone+marrow+mesenchymal+cells+in+moderate+and+severe+knee+osteoarthritis+is+safe%3A+a+phase+I%2FII+study
(Intra-articular injection of expanded autologous bone marrow mesenchymal cells in moderate and severe knee osteoarthritis is safe: a phase I/II study)
The study in the above link demonstrates to me the safety, feasibility and efficacy (in a small study) of utilizing EXPANDED or cultured autologous stem cells. A practice that regenerative clinics (or predatory clinics depending on your bias) are not allowed to engage here in the United States.
Results
No severe adverse events were reported up to 24 months follow-up. Normalized KOOS improved significantly. MEAN KNEE CARTILAGE THICKNESS MEASURED BY MRI IMPROVED SIGNIFICANTLY. (Capitalization mine)
To me, this study demonstrates that less than desirable results of regenerative treatment in the U.S. may have far less to do with any particular clinics’ practice of medicine. Less than desirable results are perhaps more a reflection of how these U.S. clinics have been hamstrung by arbitrary rules about what constitutes a drug and the interference into the practice of medicine by a government agency that never had that specific mandate to begin with.
According to the editor….”There needs to be more rigorous data on efficacy.”
More importantly, the FDA needs to get out of the business of regulating the practice of medicine and allow this field to flourish. As of yet there is nothing near the equivalent relative to Induced Pluripotent or Embryonic Stem Cells in terms of their therapeutic value. Lots of papers. But not much else.
Douglas, This kind of study is very weak scientifically. With 13 patients and no controls it doesn’t have the power to figure out anything clearly and it was non-blinded it seems so that introduces potential bias. If stem cells for arthritis really works, then large, double-blinded and properly controlled studies should prove that.
What kind of stem cells were used? and what is KA34 see CIRM-study?
According to CIRM´s Grants Working Group Public Review Summary, KA34 is a small molecule drug to be administered by intra-articular injection, which promotes the differentiation of cartilage MSCs into chondrocytes through increased chondrogenic gene expression.
The main problem, again, is conflating the term “stem cell” treatments with every possible injectable that is being used to treat knee pain. Can we all finally state that the majority of cell clinics are in no way using MSCs of any sufficient therapeutic numbers or viability to even qualify as a “stem cell” treatment.
We need to call these hyped up treatments something else so that the term “stem cell” treatment is reserved for those clinics/labs that are actually using autologous MSCs and documenting Elisa counts, CFUs, viability,under an IRB and are following their patients closely and recording that data whether or not the patient is paying for the treatment as part of a trial or if it is a sponsored trial.
Paul, I enjoy reading your blogs and I learn a lot but please take the lead and stop calling these sham clinics and studies “stem cell” related because they are not.
I agree there is no solid evidence that these types of “stem cell” therapies help knee pain from Osteoarthritis.
I am surprised no mention of this paper from Mayo Clinic group: Am J Sports Med. 2017 Jan;45(1):82-90. doi: 10.1177/0363546516662455. Epub 2016 Sep 30.
They injected BMAC into one knee and saline into the other, and blinded the patients. From their summary (https://news.mayomedicallaboratories.com/2016/12/09/mayo-clinic-finds-surprising-results-on-first-ever-test-of-stem-cell-therapy-to-treat-arthritis/): The findings in The American Journal of Sports Medicine include an anomalous finding—patients not only had a dramatic improvement in the knee that received stem cells, but also in their other knee, which also had painful arthritis but received only a saline control injection. Each of the 25 patients enrolled in the study had two bad knees, but did not know which knee received the stem cells. Given that the stem cell-treated knee was no better than the control-treated knee—both were significantly better than before the study began—the researchers say the stem cells’ effectiveness remains somewhat uninterpretable. They are only able to conclude the procedure is safe to undergo as an option for knee pain, but they cannot yet recommend it for routine arthritis care.
2 possible options: 1) The “stem cells” homed to the other side to help relieve pain on the knee that got saline, or 2) This is all placebo effect or a non-specific effect due to injections. I favor the 2nd interpretation, though of course, no way to really know for sure from this (and other) limited studies.
Thanks, Dan, for the comment. I’m glad you brought up that article. It’s not one that came to mind as I was writing. While apparently a few stem cells can leave even discrete spaces like joints post-injection, I have a hard time imagining reasonable #’s of cells going from one knee to another so I’m thinking this is likely a placebo effect. Circulating adipose cells aren’t likely to live long either.
Why wouldn’t the Mayo article come to mind? I’m a triathlete facing the prospect of not being able to run anymore which is just not acceptable! The first thing that pops up in my Google search is the Mayo study.
This should be reiterated over and over again:
“The bottom line in my view is that stem cells for arthritis from clinics directly marketing to consumers is most often going to be a big waste of money for patients.”
In my opinion, if you’re not getting an opinion from two orthopedic surgeons who know immunology and stem cell biology, you’re throwing your money away. Demand cell counts and ELISA on what you’re getting back.
Paul, You have mixed apples with oranges. Two papers about osteoarthritis and about third rheumatoid arthritis. Over the years I’ve looked at a good number of papers pertaining to all sorts of treatments for osteoarthritis, including publications about conventional orthopedic surgical treatments that actually cause osteoarthritis!
There is rather a lot to consider. I would agree, however, that, so far as I have been able to determine, presently there is no cure for knee osteoarthritis — although there are many types of disease-modifying treatments/behaviors, for both the better and the worse.
Correct me if I’m wrong, but the authors of this paper about a “patient’s perspective” don’t seem to be patients. Indeed, most of them have affiliations that indicate “orthopedic surgery”. I’d not be inclined to see them as neutral investigators.
A cynic might say that the title of the paper borders on sneaky marketing that is reminiscent of, well, of disreputable clinics… Personally, I suspect that it may be more a case of thoughtless arrogance.
Hi Brian,
Yeah, good point that the last study I mentioned was rheumatoid. I was just trying to find recent controlled studies arguing for a benefit for arthritis generally, but we should keep osteo and rheumatoid separate to some extent in our thinking…although I think clinics are out there selling for both.
And, yep, my first reaction to the “patient perspective” part of the title of their paper was to be puzzled as it didn’t seem to fit with the paper itself. I should have mentioned that in the blog post. I might do an update.
Stemcell treatment should be provided in regular hospitals and it should be done by specialists in the e.g. neurologists ,orthopedists, dermatologists, etc.