A Review of the Harrell Paper on Marrow Cellution (Maxx Regen) Device

POSTED ON 4/25/2017 IN Industry News BY Christopher Centeno

These past few days, my LinkedIn post of the issues with the Marrow Cellutions white paper has blown up with upset sales reps who vend the device. During that back and forth, another paper put out by the company was brought up, one by Harrell et al that seemed to show that the device was capable of producing twice as many stem cells as a commonly used bedside kit. So this morning I'll review that paper as well.

What Are We Talking About?

When doctors draw bone marrow aspirate for a stem cell procedure, they use what's called a trocar. Basically, a type of specialized needle. In the past few years, a device has entered the market that purports to be a better trocar. That device is known as the Marrow Cellution (MC); more recently it has been private labeled and is also called the Maxx Regen. When the device entered the market, it was supposed to be used as a substitute for a standard trocar (usually called a Jamshidi). However, doctors soon balked at the price as the MC costs about 20 times more than the simple disposable trocars that usually help physicians draw bone marrow! So the company refocused their marketing strategy, and the MC became a way to replace the bone-marrow-concentration kits many doctors use.

Once the bone marrow aspirate is drawn (it looks like thick blood), the doctor then usually places it in a proprietary kit that goes into a bedside centrifuge. That system is capable of concentrating the stem cell fraction in the marrow, which is then reinjected into the patient. We've never done that at Regenexx; instead, we use proprietary processing protocols that allow us to concentrate the stem cells further. However, almost all physicians outside of the Regenexx network who offer bone-marrow-based stem cell procedures use these kits.

What's interesting is that the MC device is now being sold as a way to skip the concentration step. The manufacturers claim that their device can concentrate stem cells just because of the way it draws bone marrow, so there is no need to purchase a kit to further concentrate. To support that idea, they have sponsored a few papers. I reviewed one of these advertising white papers supporting the Marrow Cellution device a few days ago. Another one, which I have known about for a while, came up during the LinkedIn discussion. That paper was produced by Harrell et al, and I'd like to review it this morning.

The Harrell Paper on the Marrow Cellutions Device

While the Scarpone white paper I reviewed a few days ago made the error of not performing a head-to-head comparison between the MC and the other devices tested, the Harrell white paper (i.e., not published in the peer-reviewed literature but instead used by a company as advertising) focused on one competitor device to the MC and didn't make that error. It compares the MC device versus a commonly used bedside bone-marrow-concentration system known as the Harvest Technologies Smart PReP 2 (Harvest). Not surprisingly, the Harrell paper concludes that the MC device without additional concentration gets more stem cells than the Harvest machine that concentrates cells. How is this possible? Likely with some research sleight of hand. Let me explain.

We've known since the 1990s that when drawing bone marrow, the first few milliliters (ml) taken have the highest concentration of stem cells. After that, the stem cell concentration steadily declines. This is why at Regenexx, we've taught our network physicians to take low volumes of marrow from many sites to maximize the number of stem cells. Regrettably, many physicians outside our network routinely take shortcuts in drawing marrow. For example, a common draw technique used is to go into a single site and draw 20 ml of bone marrow aspirate (BMA), move the trocar a bit deeper and draw 20 ml, and then do that a third time and draw another 20. Another common technique is to only go to one side of the pelvis and draw 3 X 20 ml sites. Hence, Harrell tested this last method against the ultra-low volume pull of 8 ml used with the MC device.

The most interesting thing about the paper is that despite taking the 60 ml and concentrating the stem cells, there were twice as many stem cells (as represented by CFUs) in the MC bone marrow product as there were in the Harvest product! How is that possible? While that result might seem revolutionary, it's really expected based on two things: the dramatic difference in the marrow draw technique and the fact that the Harvest machine is pretty poor at bone marrow concentration.

Explaining the Research Sleight of Hand

In a good magic trick, you're distracted by something over here while the magician does something over there you don't notice. So while the Harrell paper has physicians distracted with scientific jargon, like CFUs, TNC, and so on, they won't notice that it violated one of the most sacred scientific principles by altering too many variables. Let me explain.

While Harrell did a good job of comparing the typical substandard draw out there to the MC device draw, he altered at least two variables to do it. In a lab paper like this, you usually only want to alter one at a time. In this case, he changed the device (switched out a standard trocar/Harvest with the MC device) and the marrow draw technique (3 X 20 ml versus 4–8 X 1–2 ml draw).

So like a good magic trick, what went into the Harvest machine for concentration looked like the same thing that the MC device had drawn, but it was really something very different. You see, Harrell had drawn 1–2 ml up to 8 ml as he retracted the MC device. In fact, he could have drawn as many as eight times. The Harvest BMA only included three draws. Each of these pulls produced the most stem cells in the first few 1–2 ml. After that, there was a declining number of cells and an increasing amount of non-stem-cell contamination. Hence, Harrell may have pulled more stem cells not based on the magic of the MC device, but because he used a much better technique (i.e., more pulls with lower volume in each draw). Add to that that the Harvest machine isolates the stem cell fraction and then adds back in 70–80% contamination (i.e., red blood cells and other things that aren't in the stem cell fraction) and you get what you see.

So while Harrell answered the question of whether the MC beats a substandard draw using a Harvest machine, he didn't answer the bigger question. What's that?

The Big Question

To me, the big question is whether a standard trocar drawing using the same ultra-low volume technique used by the MC can produce the same stem cell yields. Meaning is there something special about the MC device to warrant its high cost, or is the real slight of hand forcing doctors to perform a high-quality draw? If it's the latter, the company has no product to sell. Which is why they're likely so darn nervous about the independent testing we're about to perform. On the other hand, if it really works through some magic of the device, then our medical network could well be the largest customer they have.

This past February at the IOF conference, I approached the MC rep at the conference and asked if they would sample some of these devices for a test performed by our lab. This is because, at Regenexx, we test everything at our expense before deploying it in the network clinics. This is to see if it really does what it claims. This is how we exposed the amniotic and cord "stem cell" scams sweeping the nation. We tested to see if these products really had stem cells—they did not.

This conversation turned into e-mails. Regrettably, the rep I talked to was just a middleman in a long chain of sellers and resellers of the device. Eventually, the rep's enthusiasm was shot down by corporate who didn't want us testing the MC device. I then contacted the decision makers, giving them the opportunity to have a rep in our clinic to supervise the test as well as to take some of the bone marrow to be tested in a lab of their choice. They didn't seem to like the fact that we were viewing the device as a way to get more stem cells from a marrow draw and then we wanted to concentrate further. Why? If the device is just a fancy trocar, it's worth far less than if it replaces the need for a bone-marrow-concentration kit. So we got nowhere, and the company went so far as banning us from buying the MC device to test. However, we managed to secure several through third parties, and we have our test set up for May.

So will the MC device work? How will it fare against a simple trocar replicating the same low-volume BMA approach? If it does work to get more stem cells, then we will certainly take whatever it produces and further concentrate cells. However, I have my doubts that it will produce more cells than a simple trocar used in the same exact way.

The upshot? While I wasn't planning on blogging the Harrell paper, it's always good to get fired up by a spirited discussion. After all, this is how science and medicine advance. Physicians asking questions and questioning what's being sold to them is a good thing!      

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