If you read this blog, you know that I tend to blog about what happens in daily practice. Hence, I just learned of a new spine-treatment approach from a patient who asked me to review his medical records to see if I could help his long-standing low back pain. In the records, it was called BioDisc, and the first thing that I thought of was an old phrase, “everything but the kitchen sink.” In fact, I want to send out a plea to my learned colleagues with this blog: “Please don’t throw the orthobiologic kitchen sink at your patients.” Let me explain.
Treating Low Back Discs with Stem Cells
Way back in 2006, I first injected a disc with bone marrow concentrate and then later that year with culture-expanded stem cells. I’m pretty sure that I was the first human to do either of these procedures. The good news was that this was a first; the bad news was that since I chose the wrong patients (all had severe degenerative disc disease) and used the wrong technique, I saw little results. Then in about the latter part of 2007/early 2008, we had a breakthrough by changing what we injected and how. What this experience taught me was that who you treat and what you inject into the disc and how you inject it matters. In the 12 years since then, nothing has changed my mind about that. In fact, our experiences with injecting things into discs have only reaffirmed this observation.
The Low Back Disc Stem Cell Wild West
These days, it seems that we have at least hundreds (if not almost a thousand) medical providers who are injecting all sorts of stuff into the disc. While I welcome the company, as I have repeatedly said on LinkedIn discussion boards on the topic, injecting the disc is always a higher risk endeavor because of the risk of a nasty infection called discitis. This rare issue, if it happens, can require surgery and IV antibiotics. Hence, we should stay out of the disc until we’re absolutely sure that the disc really needs to be treated to ensure success.
By using this “extra-discal” approach, we have helped countless patients with low back pain by focusing on all parts of the functional spinal unit (the facet joints, ligaments, stabilizing muscles, nerves, and tendons). We often don’t even need more expensive and invasive stem cell procedures as most patients do fine with just blood platelet approaches. However, for this to work well, we have developed a number of different protocols that are used in patients with different problems. To learn more in depth about what we do and why, please see my video below for more details:
Disciplined Orthobiologic Approaches
While we have seen many things that make little sense injected into the disc, the medical community really only has experience with a few orthobiologics. Meaning these basic types of injectates have been shown in animal models to work, and there is some early human evidence (that goes beyond a handful of cases) that looks promising:
- Platelet-rich plasma
- Bone marrow concentrate (a same-day bone marrow stem cell procedure)
- A2M-enriched plasma
- Culture-expanded bone marrow stem cells
- Stromal vascular fraction
The first three are allowed in the U.S.; the last two are not permitted. Why do I call these “disciplined” approaches? They only use one big category of orthobiologic, and they all have some published data.
The Kitchen Sink
OK, now we come to what drives me a bit crazy and what has me concerned about my legacy of orthobiologic disc work. I was asked to review the medical records of a patient who traveled from the Southwest to the Northwest to get a low back disc procedure. When the patient contacted me, he described that this clinic had already tried a low back stem cell procedure. Given that he had some improvement but not nearly as much as he had hoped, I agreed to look over his records to see if I could help further.
I had been on vacation, so I finally got a chance to sit down yesterday to see what he had done, and I must say that even I, who have observed some crazy stuff, was shocked. The procedure, in the notes, was called “BioDisc.” Here’s what was injected/performed:
- Nucleated Cell Particle Stem Cell Isolate
- Peripheral Blood MSCs
- Radiofrequency Ablation of the Disc Annulus
- High-Dose Epidural Steroid Injection
- Autologous Fibrin
- Platelet-Rich Plasma
- Platelet Releasate
To begin with, let me start with the biggest “no-no” on the list. High-dose steroids kill stem cells dead. This is well published, and we first observed this in the lab back in 2008. Hence, we won’t allow our patients to be injected with them within 6–12 weeks of any platelet or stem cell-based procedure.
This patient also never got any or many stem cells, despite number two and three above. First, there are no (or extremely few) circulating mesenchymal stem cells (MSCs) in the peripheral blood. I know this firsthand as back in 2008–9, we were asked to try to isolate mesenchymal stem cells (MSCs) from apheresis blood collections for a private company that used a very sophisticated technique to try and mobilize MSCs out of the bone marrow and into the bloodstream using a heavy-handed chemical drug. We got nothing, despite many attempts. While one or two studies have claimed to be able to isolate very few MSCs from blood, this provider records an MSC count of 375,000,000 from about 100 milliliters of peripheral venous blood! This tells me immediately that this provider doesn’t know what he doesn’t know.
So let’s take the 375 million number above as an example of how nutty this treatment really is at this point. As an example, we know that there is a very high concentration of MSCs in your bone marrow and almost none in your blood (the latter is where this doctor claims to have obtained 375 million). So let’s run some quick calculations. In a 60 ml bone marrow aspirate, if you use an impeccable technique in drawing the marrow and processing it, you can get somewhere on the order of tens of thousands to 100,000 MSCs in a very healthy, fit, and active male. Last I checked, 4% of your body mass is bone marrow. Hence, if this patient weighed 80 kg, we can multiply 80 by 0.04 to get 3.2 kg of bone marrow. Given that bone marrow aspirate is mostly water, we can roughly convert 3.2 kg to 3.2 liters of bone marrow aspirate. Having said that, there is also fat in bone marrow, which is less dense, so most citations quote about 6 liters of bone marrow available. If we see how many times 60 ml goes into 6,000 ml, it’s 100. Hence, we multiply 100 by 100,000 (we’ll use the high number) to get roughly 10 million MSCs in his whole bone marrow space. Hence, the idea that you could get 375 million MSCs out of a few hundred mls of blood is ridiculous. You likely don’t have 375 million MSCs in all of the tissues of your body.
What is a “Nucleated Cell Particle Stem Cell Isolate”? I can really find no published scientific data on what this is, let alone anything published even in a rat that would tell us whether this would help discs. My best guess is that what’s being referred to here is something like a very small embryonic-like stem cell (VSEL), which is supposed to be a non cell small particle that can give rise to the instructions for stem cells. However, this idea that these particles exist was debunked in the scientific literature.
Radiofrequency ablation of this disc annulus was also performed. What’s this? This is inserting a probe into the outer portion of the disc and burning the fibers. Why would you want to burn fibers that you’re trying to repair? Your guess is as good as mine.
The collagen used is CellerateRx, a bovine type-1 collagen. The disc annulus contains type-1 and type-2 collagen, so not sure why you would only want to use type 1. This idea here is that you’re providing a scaffold on which stem cells can grow, but as I’ve already established above, no stem cells were used in this procedure. I also ran a search of the US Library of Medicine under type-1 collagen and intervertebral disc repair. Suffice it to say that we have no animal or human data on whether injecting type-1 collagen into a disc does anything.
Autologous fibrin was also injected. I have already blogged extensively on the clinical trial that showed that autologous fibrin injected into the disc was ineffective. This procedure was called “DiscSeel” and flubbed its FDA-approval trial. Hence, it’s unknown why this is being injected.
The platelet releasate is a growth factor-poor version of the platelet lysate we’ve been using forever in and around the spine. We did publish on injecting platelet lysate epidural (outside the disc), but a releasate is the poor cousin to that product. In addition, this guy doesn’t have the same problem for which we used that treatment.
Finally, we get to the only two things that have some clinical data that shows that they might help discs. These are the PRP and the A2M. However, for the former, while there is a randomized controlled trial by Greg Lutz out of HSS, that didn’t also include burning the disc, injecting high-dose steroids, collagen, fibrin, and a few other kitchen sink items. For A2M, there was just a small case series published that seemed to look promising, but that was only in patients who had been tested to be FAC+ based on a prior disc wash, which is not a test I can find has been run in this patient.
Conclusions and a Message to My Colleagues
Dear colleagues, please don’t be a nut who doesn’t know what he or she doesn’t know. Meaning, orthobiologics have great promise to help patients with spinal pain. We see it every day. In addition, I get that we all want to experiment a bit to help that unique patient, and frankly, that’s what you’re licensed to do as a medical doctor. You get paid the big bucks because you are permitted to make intuitive leaps to see if X and Y might help a patient when neither X nor Y has ever been used in that way. However, when that devolves to trying X, Y, Z, A, G, J, I, P, Q, and U all at the same time, what might be a possible good thing becomes an undisciplined mess. In addition, when you’re claiming that 100 cc of peripheral blood has more MSCs than exist in the entire body, the trend of taking a weekend course and claiming to an expert has gone way too far. This particular provider must have fallen asleep in basic biology.
The upshot? This procedure was destined to be less than optimal for all sorts of reasons. Having said that, it may even provide some patients relief. That didn’t happen in my patient. Thankfully, this guy has the financial resources to laugh this off and move on, but for many patients, this may end up being their life’s savings spent on an undisciplined mess of a therapy. As I always say, please be careful out there and buyer beware!