New Knee Arthritis BMC Study Adds More Confusion

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arthritis stem cell research

It’s hard for patients to understand that in some fields, academics are way behind their private-practice counterparts. One of those fields used to be interventional spine care, but the academic system eventually caught up. One of those right now is regenerative medicine, where academics are, for the most part, just figuring out which end is up. This can cause some problems, like issues that I’ve found with a recently published paper on the use of a same-day bone marrow stem cell procedure (BMC) for knee arthritis. So let’s review this recent paper.

All Stem Cell Procedures Are Not the Same

Before we get into this recent paper, let me go over the different components of a stem cell procedure that separate a novice from an expert. Why? Regrettably, most of my academic counterparts are still novices. Here goes:

  • Drawing stem cells. How you get your stem cells is critically important so that you get the maximum dose of cells. The most common type of procedure used to get bone marrow stem cells is a single-site draw, and more than 90% of physicians who perform same-day stem cell procedures use that method. However, we’ve known since the 1990s that this reduces stem cell yield. Below is my video on all of the things you need to know to perform these procedures like an expert.
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The New Same-Day Stem Cell Knee Arthritis Study

First, it’s always great to see more research on stem cells and knee arthritis, so it was great to see this new one. In this small study, published in the American Journal of Sports Medicine, the authors treated 25 patients with bilateral knee arthritis with bone marrow concentrate (BMC, or a “same day” stem cell procedure) in one knee or a saline placebo injection in the other. The patients were only followed for six months, but the BMC-treated patients didn’t report any more relief than the saline-treated patients? Hmmm…Given that this isn’t consistent with our experience over the last decade-plus, let’s dissect what was done in the study. Here are the issues I see:

  1. While the authors claim that they used BMAC (same as BMC), what they actually used was a different animal, BMC plus large volumes of PPP (platelet poor plasma).
  2. The total cell count of the concentrated bone marrow was very low, and the authors diluted this still further. As an example, after placing the bone marrow in a machine, they ended up with 6 ml to inject, which is about triple the size of the actual stem cell layer (which means they had lots of red-blood-cell contamination). More concerning is that they then added a whopping 10 cc of PPP. So if the concentration of stem cells per cc was X to begin with, it was three-eighths X once they injected. Why is this an issue? Multiple studies show that the concentration of stem cells in the knee or on a cartilage lesion is likely related directly to outcome, so by diluting the number of cells per cc, the authors may have reduced the efficacy of an otherwise helpful procedure.
  3. The concentration of cells injected was very low. The paper lists a mean of 16 million “total MNC” count (which is a subpopulation of the total nucleated cells [TNC]) in the final product injected. They don’t list TNC, which is the only metric reported in the literature right now that’s been associated with a dose-response in knee arthritis (see our paper on stem cell dosing in knee arthritis). How do we convert “total MNC” to TNC? One paper discusses a conversion factor of about 50% (total MNC + approximately 50% = TNC). Hence, if we take their 16 M cells per ml and add 50%, we get a TNC of about 24 M cells per ml. If we multiply that times 6 (because on average 6 ml was injected), then we get a TNC of 144 M. Even if we round up, this paper used significantly less than the 400 M TNC per knee that we defined as the lower limit for a positive pain outcome in our paper.
  4. The bone marrow aspirate technique was not the best for maximizing yield. Near as I can tell, they used a single puncture site and withdrew 26 ml of bone marrow and redirected the trocar three times. So through a single cortex site, they drew three X 8–9 ml. We know based on multiple papers that lower volumes from multiple cortex sites produces more cells (see video above).
  5. They used the wrong anticoagulant for bone marrow. In our experience the ACD they used is a poor anticoagulant for bone marrow as it often produces clots. Since they used a machine to process the bone marrow, they would have no idea if they had clots in the marrow. However, clots rob cells, so this may be one of many reasons the number of re-injected cells was low.
  6. The choice of treating bilateral-knee-arthritis patients was not ideal, as our registry research has shown that patients who have three or more joints involved don’t fare as well with these procedures, likely due to a systemic stem cell problem. While they don’t report any info on other joints, it’s likely a safe bet that a significant portion of patients with bilateral knee arthritis have arthritis in other joints as well.
  7. The authors didn’t rule in or out other causes of knee pain. Given the recent research on the number of patients undergoing knee replacement who do more poorly because they have a low-back problem, this could be a problem.
  8. The fact that one side was used as a treatment and the other as a control is a big “no no”. Let’s think about this practically. If I have one knee that got treated and swells after a stem cell injection (common) and the other doesn’t after a saline injection, the test subject will know which knee likely got the placebo. This then invalidates the “blind” part of the study. In addition, any positive or negative changes in one knee impacts the other with regard to activity. Suffice it to say that while this study deign was likely chosen because it made recruitment of the study faster, it’s a bizarre and problematic way to perform knee arthritis research.

There are other issues with the study, but those are the big ones. Again, one of the problems that we see is that we have many physicians who learned their craft from a weekend course and thus make basic errors. In their push to expand kit sales, manufacturers of bedside units have tried to distill procedural education to a few hours, which only reduces the likelihood that these procedures will be effective.

The upshot? I’m not sure that this study tells us much other than a strange variation of a low-cell-count, same-day stem cell procedure where the cells are combined with 10 cc of PPP when used in patients with bilateral knee osteoarthritis (OA) didn’t seem to work. I look forward to other studies!

This blog post provides general information to help the reader better understand regenerative medicine, musculoskeletal health, and related subjects. All content provided in this blog, website, or any linked materials, including text, graphics, images, patient profiles, outcomes, and information, are not intended and should not be considered or used as a substitute for medical advice, diagnosis, or treatment. Please always consult with a professional and certified healthcare provider to discuss if a treatment is right for you.

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13 thoughts on “New Knee Arthritis BMC Study Adds More Confusion

  1. Louise Casey

    Stem cell is used for arthritic knees. Is it used when meniscus is gone or badly torn. Or in bone in bone?

  2. Bill Last

    I am 69 years old. I am interested in trying stem cells in my knee. I had them (not my own) injected into my hip but it did not work. I later found out that the doctor used only 10 million cells and should have used 50 million. I ended up getting a new hip. I now have arthritis in my left knee and do not want to go for a replacement. Cortisone does help. I have arthritis in my lower back and just had a fractured disc (L5) cemented.

    1. Regenexx Team Post author

      We’d be glad to help. Please submit the candidate form so we can take a look at your MRI’s and medical history and can get on the phone and chat. Unfortunately, “not your own” stem cells can’t help, regardless of the number. But important presently, Cortisone shots might help with the pain, however they escalate the situation as they kill the local stem cells as well as tissue. Interestingly, L5 and knees are related:

  3. Sam

    Certain regenerative medicine providers offer IA injections with dextrose to treat OA. What are the pros (if any) and cons of such injections?

    1. Regenexx Team Post author

      The dextrose in Prolotherapy brings no regenerative potential of it’s own but stimulates temporary inflammatory or healing response by deliberately creating a micro-injury. It’s widely used to tighten lax ligaments, etc. and is the oldest regenerative treatment. We’ve used it very successfully for many years. But for OA, what exactly are they causing the micro-injury to? Blind IA injections somewhere into the joint are unlikely to do any good no matter what’s being injected and there is the risk of damaging other structures. In regenerative medicine the trick is to match the right treatment to the right problem, and to be able to get what you’re injecting precisely where it needs to go.

      1. Sam

        I also don’t understand what they are trying to achieve. They just dump dextrose into joints (e.g. Knee, SI, facet) with the idea that it is good for cartilage regeneration and pain. But as you mentioned when they are not even hitting the cartilage to cause micro-injury then it has no regenerative potential. So essentially a patient undergoes an invasive treatment without any joint regenerative efficacy.

        1. Regenexx Team Post author


          Not sure what the goal is either…

          1. Lily

            Is there a good stem cell treatment for kidney disease? I am Stage 4 and am stable at this level. However, I am chronically anemia and have chronic high blood pressure which depletes my quality of life and leaves me in fear of needing dialysis or kidney transplant. I would like to avoid this so I am curious if there is a stem cell treatment to improve my symptoms and avoid dialysis if I take care of myself. What about stem cells coming from the umbilical cord from the birth of a baby?

          2. Regenexx Team Post author


            We only do research on and treat orthopedic injuries and conditions with stem cells and platelets. You can generally search for advances in other fields on Pubmed or Google Scholar.

  4. Debra

    I have had 2 Bone Marrow Stem Cell transplants for a grade 4 osteoarthritis in my knee. Had great results but only lasted about 3 months and then pain returned. Would your procedure produce better results, if so how? Have done the PRP, arthroscopy with washout then viscosupplement injections(6). Once again excellent results, no pain , no cane for about 4 months. I am under the impression that even stem cells can’t give me the cartilage my knee needs. Again can your procedure any better results.

    1. Regenexx Team Post author

      To answer that question for any particular case an exam or a Candidacy evaluation would be needed. To answer the question generally, there are great differences in results with Regenexx because of the differences in the procedures based on extensive research, the exams, and the training and the experience of Regenexx providers. and Arthroscopy is a net negative, hyaluronic acid injections really just supply lubrication. Stage 4 Knee OA is a vicious cycle in which the inflammatory response from tissue breakdown causes more tissue breakdown, so that nasty chemical environment needs to be turned around. Cartilage loss in of itself does not cause pain, the effect of the nasty witches brew on nerves does. Importantly, in addition to treating the OA itself, the causes need to be investigated and treated so that healing can take place. Causative and contributing factors could be things like a low back nerve misfiring, unstable ligaments or tendons, missing pieces of knee anatomy from arthroscopy, instability in a hip or ankle, etc. If you’d like to see if you’d be a good Candidate for a Regenexx procedure please submit the Candidate form.

  5. Peter

    I read this Mayo clinic study. The author appeared stunned by how well the “BMC” worked. I didn’t consider it a negative at all. The Mayo clinic continues to offer Bone Marrow procedures in Minnesota and describes them as efficacious.

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