This past two years, we’ve seen an explosion in off-the-shelf products claiming that they have live stem cells. It’s really somewhat of a mystery why this is happening, as just the claim that a quickie online-registered product has live cells makes it an illegally marketed drug product. Throw in that the data produced by the company usually doesn’t support the claim that live and functional stem cells are present and you have a real head-scratcher. This was the case when I reviewed the INVITRx Pro Cord Blood product. Let me explain.
The 361 Bait and Switch
If you want to sell a cell-based tissue product that contains no live cells, you can get away with a 45-minute, quickie online registration with the FDA. This is not an FDA approval, but an honor-system registration. There’s just one problem: if you claim that the product has live cells, it can no longer live under the quickie registration, but, instead, it’s a cell drug that must go through a 5- to 10-year cell-drug approval process costing tens to hundreds of millions of dollars. So why would anyone in their right mind claim that there are live cells in their product? Because it pushes sales and price. Watch the video below for more information:
Doctors these days are looking for stem cells to use in their therapies. Many don’t want to take the time and energy it requires to learn how to harvest stem cells from bone marrow, and as a result, they want an off-the-shelf version. There’s just one problem: there is no such live stem cell product that has been approved by the FDA for orthopedic use. When it comes to cord-blood stem cells, only one product exists that does have an FDA approval, and it’s only released by the tissue bank to treat pediatric cancer.
This creates a conundrum for tissue processors. Doctors aren’t interested in cord-blood products that don’t have live stem cells. The manufacturers aren’t allowed to claim that their products have live stem cells. Hence begins a game of cat and mouse with the FDA. Most companies are smart enough not to place any information about live stem cells on their websites. Some just don’t care, and when that happens, they all take a similar tack but with some unique twist. The manufacturers of INVITRx Pro have taken that same tack with a unique twist.
Could This Product Even Have Live Stem Cells?
Before I get into how this product has chosen to evade the above FDA regulations, it’s best to get right to the multibillion-dollar question: does this product have stem cells? After all, that’s what physicians are looking for. The company has produced a white paper curiously conducted at the same lab at which I have seen other such tests conducted. So let’s dig into the science behind that information.
First, from the introduction found in the white paper conducted by DaVinci Labs, the focus is on cord blood and then quickly turns to mesenchymal stem cells (MSCs). So while the white paper states that it tested a vial of the “Invitrx regenerative medicine product,” it’s clear that is their cord-blood product. As you watch the video above, I cite three papers that show that it would be very unlikely to find any mesenchymal stem cells in this product. Why? The authors of the white paper fail to mention that the mesenchymal stem cells don’t live in the cord blood. See the video below for more info:
Does the White Paper Prove There Are Live Stem Cells?
First, the white paper goes into simple live/dead viability testing. Regrettably, as I have discussed in the past, this tells us nothing about the overall health of these cells. Why? See the video below for more info on that topic:
The viability reported is a poor 75%. Why is that poor? Normal viability for adult stem cells properly stored, thawed, and recovered is 90%+. Hence, we know that these cells have been through heck and back, and the onus in on the author of the white paper to show that they can survive past the thaw. That would require testing in culture, which wasn’t done. However, it may not make a difference as we wouldn’t expect there to be any mesenchymal stem cells in this product, and the white paper doesn’t disappoint in that regard.
If you watch the video at the top of the page, you will see why the authors of the white paper failed to test the cell-surface markers that actually identify mesenchymal stem cells. While they quoted the key paper published on the topic, they then threw that publication out the window and never tested all of the markers required. Hence, the flow cytometry testing in the white paper is for show as it’s incapable of finding MSCs. In addition, they failed to do the other tests needed to ID an MSC, like plastic adherence in culture or trilineage differentiation. That’s likely a good thing, as the research shows if they had run the proper tests, they would have been very unlikely to find any MSCs in cord blood.
How many stem cells of any type are in this sample? The only stem cells identified weren’t mesenchymal but hematopoietic stem cells (HSCs). These blood-forming stem cells may be helpful for certain orthopedic applications. However, there were very few of them. As in the video, when you do the math, the number of cells that are present are about 1/20th of the amount normally found in autologous bone marrow concentrate from an adult patient.
The INVITRx Pro IRB Twist
OK, now for the kicker. So far we have a company that isn’t allowed to go through a quickie FDA tissue registration and claim live stem cells. In fact, that’s what they’re doing. To add injury to insult, they hired someone to test for mesenchymal stem cells and the testing wasn’t capable of finding any of those cells. In fact, the outside published research shows that we wouldn’t expect there to be any in this product. Finally, the only stem cells identified in the product were HSCs, but this number was far fewer than can be had by a simple bone marrow stem cell collection and concentration procedure performed in an adult patient. However, it gets worse, much worse.
How does the company justify violating FDA rules on marketing this as a stem cell product? It appears the strategy is through having multiple “IRB approved” studies. The problem is that since they claim that there are mesenchymal stem cells in the product (a hollow claim based on the above analysis), then these research projects must be full FDA drug studies. Meaning they wouldn’t be permitted to offer these cells for sale until those studies were complete. They seem to try to get around this by offering to pursue an IRB for the physicians who want to pursue purchasing their drug product. There’s just one little problem. I’ve seen that dodge before.
About 1–2 years ago, I was contacted by a local tissue bank that had cord blood for sale. The sales rep swore on a stack of bibles that it was legal for him to sell and for me to purchase this for orthopedic use. I knew better, so I told him that if we used it, it would have to be through a drug study. I then asked to speak to the medical director. When I confronted him, it was clear that he understood that my use of this product would require an FDA-approved drug study costing a few million dollars, just to start, for each and every indication (e.g., knee arthritis would be one study and shoulder rotator cuff another). The company wasn’t able to fund such studies, so the conversation ended.
How do we know that INVITRx has no such FDA approval for these studies? First, there are no listings for these studies sponsored by INVITRx on www.clinicaltrials.gov. In addition, I can find nothing at the FDA. So if this company has any such drug approvals (open BLAs), they should reach out to me.
The upshot? The white paper on INVITRx Pro demonstrates no mesenchymal stem cells, and we wouldn’t expect there to be any in this product. In addition, HSCs present are 1/20th of the number one would expect from bone marrow concentrate taken from an adult patient, and that assumes that all of these cells are alive, which is a big “if.” In the end, INVITRx is pursuing the same risky marketing strategy as many other amniotic and cord-blood vendors. Right now, with the FDA in crackdown mode, this is ill advised.