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What’s the Research on Knee Stem Cell Therapy?

Published on Feb 1, 2020

I’ve been both a vocal critic and fan of the bench science groups pushing one-sided news stories about the stem cell wild west. This has been a bizarre place to be given that on the one hand this space really is out of control, but on the other, the health and science reporters have trouble separating the wheat from the chaff. Now we have a new genre of story, one built to look like a scientific review of the literature for knee stem cell therapy, but it really isn’t.

The Stem Cell and Exosome Wild West

This whole space is out of control, so the fact that we have a group of bench scientists who seed negative stories is not necessarily a bad thing. Clinics offering absolutely crazy therapies without any grounding in science need to be called out and the public needs to be warned, especially given that these clinics often downplay the risks and make up the benefits.

Having said that, the news media, like a kid with ADHD on a sugar high, don’t seem to be able to tell which end is up. They can’t separate innovative approaches to medical care from offerings that are “out there”. Why? Their metaphorical Ritalin is being prescribed by the bench science crowd who doesn’t want them to make that differentiation.

Now a new news story on knee stem cell therapy is making the rounds. On the one hand, it looks like a scientific review of the topic, but on the other hand, it really isn’t. On the one hand, it did interview some academics who use these therapies, but on the other hand, it still ended up playing the exploitation card. So let’s dig in.

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The Stem Cell News Article Approach

Prohibition never works. We should have learned that in the thirties when we tried as a nation to ban alcohol. Or at least learned it in the “war on drugs”. In both cases alcohol and drug use increased. The same has been happening with news stories trying to prohibit the public from using stem cell therapies. Despite literally hundreds of news stories, the public’s use of stem cell therapies has exploded. Meaning these stories are having no net effect because they take a prohibition approach. People tend to want more of what you tell them they can’t have.

This new news story by Laura Beil is fascinating in that it tried to look at the science behind knee stem cell therapy. On the one hand, I applaud Ms. Beil for trying to dive deeper and actually including the voices of doctors who are using knee stem cell therapies on a day to day basis and not just only the same old bench scientists. On the other hand, I have to say that what looks like a scientific review of the subject isn’t close. Let’s dig in.

The Research Behind Knee Stem Cell Therapy – An Incomplete Review

Ms. Beil begins her piece quoting the usual talking heads and then distills down into what looks like a scientific review of the medical research behind knee stem cell therapy. However, a deeper review of the piece shows that it’s a very incomplete and one-sided view of the topic. Let’s review.

Ms. Beil highlights a few studies:

A Shane Shapiro study where one knee was treated with bone marrow and the other was injected with saline. I know Shane and have great respect for his work, but have already blogged on why this study didn’t actually use “bone marrow concentrate” or anything similar to the knee stem cell therapy in common use. Hence, this study wasn’t a test of the bone marrow knee stem cell therapy being used today, but of a unique therapy involving low doses of stem cells mixed with large volumes of platelet-poor plasma, or a therapy that is not in common use.
A literature review by Dutch sports medicine physicians that concluded, “All five RCTs reported superior efficacy for patient-reported outcomes…compared with controls at final follow-up (range 24–48 months). Superior radiological outcomes were found favouring stem cell injection. Superior histological outcomes and/or improved arthroscopically scored healing rates were reported in two trials. No serious adverse events were reported.” (2) So our Dutch doctors found good things about knee stem cell therapy. Given that this is a 2017 study, it only looked at the early part of the evidence base for knee stem cell therapy (through 2015-16). It did conclude that we need more high-level research.
A fat-based knee stem cell therapy trial that used cultured cells and showed superiority over placebo that was performed in Korea (3).
A study by Ken Mautner at Emory, who I also know and respect, that showed good results for both fat and bone marrow concentrate knee stem cell therapy (4).
A study by a Canadian group that used cultured bone marrow stem cells that also showed good efficacy and safety (5).

So Ms. Beil’s story included a handful of papers that almost all conclude that knee stem cell therapy works, but the overarching theme of the story continues to be one of patient exploitation. Huh?

What Was Left Out

In any argument or debate, what is left out is almost as important as what was included. This story is no different. So let’s dive into what Ms. Beil excluded:

Our 2018 randomized controlled trial which was larger than the Shapiro study and designed after the methods used in the existing knee replacement studies that showed good efficacy for knee bone marrow stem cell therapy versus PT (6). Our study didn’t make the same mistake as the Shapiro trial by treating patients with bilateral knee arthritis or using a low dose version of bone marrow.
A slew of other studies on knee stem cell therapy all summarized here (through April of 2019). In that infographic, each circle represents a study that links out to the National Library of Medicine listing or the journal website.
A slew of newer trials and studies showing efficacy.

So many other studies that should have been included in the article were left out. Why?

The Data Requirement for Medical Care is Not What Science Journalists Have Been Lead to Believe

What’s interesting about this and many other articles is that health and science journalists have this sense that all medical care requires many randomized controlled trials before being used. That, of course, is fiction, but one carefully spun by the bench science crowd. So what level of evidence is required?

Since we’re discussing knee stem cell therapy, let’s dive into knee replacement, since that’s what most patients are trying to avoid. What research do we have that knee replacement is effective? The answer is not nearly what the reporters are claiming is needed for knee stem cell therapy. Let’s dig into that topic.

You would think that since knee replacement involves amputating a human knee joint and inserting a prosthesis that we would have had great research from the start that it was highly effective. Think again. In fact, this procedure was used for decades without a single randomized controlled trial showing that it works. Then finally in 2015, one was done, comparing knee replacement to physical therapy, but the results weren’t great (7):

3 in 4 patients in the PT group who were knee replacement candidates decided not to get a knee replacement because the therapy worked so well
About half of the knee replacement patients reported some sort of serious complication
While the knee replacement patients had better functional improvement than PT patients in some tests, in others there was no difference between the two groups.
And most startling, the surgeons needed to amputate 6 knees and insert a prosthesis (knee replacement) to get one person in the study to report that they had at least 15% improved function (an NTT of 6)

In particular, we have ZERO studies where knee replacement, which would be expected to have a HUGE placebo effect, has ever been compared to placebo. So why then would these journalists require that knee stem cell therapy have many high-level studies against a placebo? Does that even make any common sense?

Separating the Wheat from the Chaff

One of the areas where journalists fail is understanding that innovative care using FDA compliant therapies that are being ethically performed and offered differ drastically from the wild west of stem cells and exosomes. In fact, a group of academics and private practitioners just finished a Delphi panel that was able to make distinctions between these two. The focus was on a legitimate stem cell therapy for knees, namely bone marrow concentrate and not the bait and switch offerings that so many clinics use with fake umbilical cord and exosome therapies. Those Delphi panel results should get published this year, so maybe then journalists will begin learning how to separate the wheat from the chaff.

The upshot? Ms. Beil’s article was only a very superficial dive into the research behind knee stem cell therapy. On the one hand, I applaud her for trying to interview academics that use stem cells to treat their patients, on the other hand, she and other journalists still can’t figure out how to conceptualize knee stem cell therapy and separate out an innovative treatment, from patient exploitation.

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(1) Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O’Connor MI. A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis. Am J Sports Med. 2017 Jan;45(1):82-90. doi: 10.1177/0363546516662455.

(2) Pas HI, Winters M, Haisma HJ, et alStem cell injections in knee osteoarthritis: a systematic review of the literatureBritish Journal of Sports Medicine 2017;51:1125-1133. https://bjsm.bmj.com/content/51/15/1125

(3) Lee, W.‐S., Kim, H.J., Kim, K.‐I., Kim, G.B. and Jin, W. (2019), Intra‐Articular Injection of Autologous Adipose Tissue‐Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo‐Controlled Clinical Trial. STEM CELLS Translational Medicine, 8: 504-511. doi:10.1002/sctm.18-0122

(4). Mautner, K., Bowers, R., Easley, K., Fausel, Z. and Robinson, R. (2019), Functional Outcomes Following Microfragmented Adipose Tissue Versus Bone Marrow Aspirate Concentrate Injections for Symptomatic Knee Osteoarthritis. STEM CELLS Translational Medicine, 8: 1149-1156. doi:10.1002/sctm.18-0285

(5) Chahal, J., Gómez‐Aristizábal, A., Shestopaloff, K., Bhatt, S., Chaboureau, A., Fazio, A., Chisholm, J., Weston, A., Chiovitti, J., Keating, A., Kapoor, M., Ogilvie‐Harris, D.J., Syed, K.A., Gandhi, R., Mahomed, N.N., Marshall, K.W., Sussman, M.S., Naraghi, A.M. and Viswanathan, S. (2019), Bone Marrow Mesenchymal Stromal Cell Treatment in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation. STEM CELLS Translational Medicine, 8: 746-757. doi:10.1002/sctm.18-0183

(6) Centeno C, Sheinkop M, Dodson E, et al. A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up. J Transl Med. 2018;16(1):355. Published 2018 Dec 13. doi:10.1186/s12967-018-1736-8

(7) Skou ST, Roos EM, Laursen MB, Rathleff MS, Arendt-Nielsen L, Simonsen O, Rasmussen S. A Randomized, Controlled Trial of Total Knee Replacement. N Engl J Med. 2015 Oct 22;373(17):1597-606. doi: 10.1056/NEJMoa1505467