I’ve covered Liveyon a number of times on this blog. Why? The company is by far the boldest in flouting FDA regulations and, despite the recent patient tragedies caused by their old product, is still chugging along. Their newest product is called the Liveyon PURE series. I’ve recently gotten a bunch of their information that I’ll review today. It’s as big a download of misinformation as I have ever seen. Let me explain.
This company has historically been known for its racy and seminude advertisements and the cast of characters in its executive team. For the former, we have:
For the latter, we have the following:
John W Kosolcharoen, CEO—John has had a number of run-ins with the law, including being banned from the SEC for investor fraud and being arrested in a Tricare fraud case. In the latter matter, John’s final criminal sentencing is still pending.
Allan Gaveck, DPM—director of education—Allan lost his license to practice podiatry in 2008 due to failure to obtain consent from the patient prior to a surgical procedure and failure to recommend that the patient obtain a vascular consultation or second opinion.
Umbilical Cord Blood Contamination
Liveyon was recently involved in an umbilical cord blood tragedy. It distributed vials of product manufactured by a company called Genetech that infected at least 12 people. This was the subject of a CDC communication as well as an FDA letter. The most interesting thing about the FDA Liveyon communication was this statement:
“These products were distributed by Liveyon in Yorba Linda, California as ReGen5, ReGen10 and ReGen30….To lawfully market these products, an approved biologics license application is needed. While in the development stage, the products may be used in humans only if an investigational new drug application (IND) is in effect. However, no such licenses or INDs exist for the Genetech-processed, Liveyon-distributed products.”
Hence, the FDA made (see link above) it very clear that since Liveyon was making the claim of live stem cells in its product (systemic effect dependent on metabolic activity) and the product was from a donor, the product was a drug that needed formal clinical trials to get approval. The problem? Liveyon only has a simple 45-minute free online registration and has no drug approval.
Could There Be Stem Cells in Liveyon’s Umbilical Cord Blood Product?
Liveyon heavily advertises that the product contains mesenchymal stem cells (MSCs). Based on all of the data published by the company to date, there has been no scientific support for this idea. While I’ll get into that in more depth below, the first question we need to ask ourselves is, does it even make sense that umbilical cord blood would have many MSCs? Nope, watch my video below for the research that shows that this would be unlikely:
The Newest PURE Series Product Information
After the IOF conference ended, I was bombarded with e-mails from colleagues who found information boxes and packets from Liveyon at their medical offices. These were laced with the term “stem cells” as well as multiple claims of healing potential. None of this is legal for a 361 registered tissue product, but this is the way the company has rolled from the outset. However, I have to say that given the above information in the FDA press release that the company needed to pursue successful FDA-regulated clinical trials prior to ever selling another vial of product, this was bold.
What is the Liveyon PURE series? The company claims that it’s a new product that it is manufactured to the highest standards. Certainly, the name can’t be a coincidence. You can’t make up a better name for a previously contaminated product that caused harm.
While I received many e-mails from many providers with lots of information, the most bizarre was a FAQ sheet that I’ll review this morning.
The Liveyon PURE Series Misinformation FAQ
There is so much bad information in this document, I have been concerned about the time commitment in reviewing it. So on a Sunday morning (and the better part of a Saturday night), I will review a few of the questions and answers from the FAQ document:
- Is it Normal to Have an Inflammatory Response After the Injection? The company admits that the nucleated cells in their product can produce an immune response in the patient since they are from another patient. This could be one of the few accurate pieces of information in the document, but frightening nonetheless. Why? We have at least one medical provider who reported a patient in the ICU after a joint injection with an umbilical cord product, and while the company claims this is not graft versus host disease, the doctors at the hospital were not so sure.
- There are multiple places in the document where it states that you should inject 4 mg of dexamethasone with the cells. We know from many different studies that steroids kill mesenchymal stem cells! So why would the company recommend injecting something that kills stem cells? It’s the blind leading the blind.
- The International Society for Cellular Therapy (ISCT) Says That the Presence of CD90, CD105, and CD73 are Necessary for the Identification of Mesenchymal Stem Cells, Why do you Only Test for the Presence of CD90? Before I get into why this FAQ answer is total fiction, please watch my video below:
The document states:
“The definition by the ISCT is for pure mesenchymal stem cells (MSCs). This product is not a pure MSC product, that would require culture expansion. It is a cord blood-derived product that contains many cell types along with MSCs. The reason we chose to test for CD90 is because it is the most widely clinically relevant marker for our purposes.”
This is PURE fiction, of course. As you learned in the video above, in order to identify a single MSC, you need the presence and absence of all markers on every cell tested. So what does testing only for CD90 only identify? Endothelial cells, smooth muscle cells, umbilical cord blood, cardiac fibroblasts, and fetal liver-derived hemopoietic cells. What does any of this have to do with positive outcomes in knee arthritis patients? Nothing. However, mesenchymal stem cells have been studied in orthopedics, which is why Liveyon hawks that the product has MSCs. However, this test for CD90 gets us no closer to finding a single MSC in the product.
- Do Stem Cells Duplicate Themselves in the Body? This is fascinating. While this document states that the cells in this product do not duplicate, this is contradicted elsewhere. Here in the FAQ document, it says that the local inflammatory response inhibits their ability to proliferate in the body, but there is no citation nor does that make sense. In fact, we hold a US patent on the idea that an inflammatory environment actually helps MSCs do their job. In another Liveyon document I received, it claims that these are young cells that double every 28 hours up to 65 generations! So which is it?
- Do Stem Cells Cause Cancer or Cause Cancer to Grow? There’s nothing like a half-truth taken out of context to make someone who doesn’t know what they don’t know comfortable. This is what the document says, “While there are no large direct studies to show that stem cells do not cause cancer, there are studies where stem cells are used to treat cancer and the conclusion is that since the cells effectively suppress cancer cells, it is believed that they do not proliferate cancer cells nor cause the formation of cancer cells.” If this was bone marrow concentrate or culture-expanded bone marrow MSCs, there are two very large studies, one by Philippe Hernigou and one by our research group, that clearly show no increased cancer rates with orthopedic stem cell procedures. However, we don’t know what’s in this soup of dead cells, so none of that applies here. The studies that use stem cells to help treat cancer all use a viral vector or a similar trojan horse mechanism to kill cancer cells, something that this product doesn’t have. The studies that inject MSCs into tumors, show that these tumors can be made bigger (in experimental animal models). However, as discussed above, we don’t know that this product contains a single MSC.
- Are Umbilical Cord Cells the Same as Amniotic Fluid? The FAQ says, “NO, umbilical cord blood cells are LIVE NUCLEATED CELLS that contain stem cells that will continue to produce anti-inflammatory and immunomodulatory components that optimize the local cellular environment. They also contain mononucleated cells that produce growth factors, proteins, and cytokines that stimulate our own tissue to regenerate and heal itself. Because the cells are LIVE, they can continue to exert these effects for weeks and even months in the body.” The problem? In order to actually determine if any of these cells in this product are alive, we would need to perform much more testing than Liveyon offers. In particular, the FACT tests would need to be performed—see my video below:
So the statement that these cells survive after thaw is not supported by any of the information that Liveyon supplies. In fact, that’s the whole point of tests done by our lab and that of Lisa Fortier’s at Cornell. None of this stuff survives to be able to propagate and function. Meaning, if you put these cells from these amniotic or umbilical cord products in an ideal environment in culture and leave them overnight and come back the next morning, they’re all dead.
- Are All Live Nucleated Cells Created Equal? The FAQ says: “No, live nucleated cells from umbilical cord blood are young, vibrant cells that have not been affected by age or disease whereas bone marrow aspirate and adipose-derived stem cells are significantly older and potentially damaged by disease. There are studies that directly compare the 3 and illustrate the superiority of umbilical cord stem cells.” Of course, there is no citation given here, which is how Liveyon rolls. How about this citation that shows that bone marrow MSCs were better than fat stem cells which were better than umbilical cord stem cells (UCSCs) for making new cartilage.
- Does Age Matter When Considering Autologous Cells? The FAQ says, “Yes, age definitely matters. In Vitro research by the International Journal of Molecular Sciences has shown that while young, vibrant umbilical cord stem cells can duplicate themselves every 28 hours for up to 65 generations or more, 50+ year old bone marrow aspirate and adipose-derived stem cells duplicate at a much slower rate of 3 to 5 days for an average of only 11 to 13 generations. Also of note is that older cells undergo senescence (aging) at a much faster rate than young, vibrant umbilical cord cells and older senescent cells produce less quantities and less effective growth factors, proteins, and cytokines.” While it’s true that younger cells grow faster than older cells, Liveyon has presented no industry-accepted data as described in the FACT guidelines above (video) that shows that its product contains any living and functional cells. Hence, dead cells proliferate less (because they’re dead) than live cells. The growth factor stuff here is false, but we’ll get to that at some point.
- Is There a Preferred Anesthetic? The FAQ claims that lidocaine does damage cells, while Marcaine doesn’t damage cells. This is actually the opposite of what’s been published. My research group published the largest and most in-depth study to date on this topic, which demonstrated that Marcaine at very low doses killed MSCs while lidocaine at low doses could harm cells. The only safe anesthetic was low-dose ropivacaine.
- What is the Best Method for Thawing the Cells? The FAQ tells you to warm the cells in your hand for 3–4 minutes and then wipe down the bottle with alcohol. This is problematic at two levels. The first is that this shock-thaw method kills cells. The proper way to recover cells is to do this in a controlled lab environment. In this easily found online tutorial by lab company Thermo Fisher, note that proper cell recovery from freezing involves cell culture (a recovery step) as thawing cells stresses cells. Why doesn’t Liveyon or any other manufacturer recommend this? Because it’s bad for business as physicians don’t have this capability. On another note, for a company that had a CDC newsletter devoted to contamination, why are they recommending a nonsterile thaw in the provider’s dirty hand and then wiping the bottle down? All of the thawing should take place on a sterile field.
- Are There Specific Numbers of Cells Necessary to Treat Different Problems? Here the FAQ provides dosing guidelines without any clinical data to support the recommended number of cells per joint. However, the document states that it’s based on 20 years of experience. Huh? Liveyon was incorporated in 2016, which gives it three years of experience with two product lines. One was recalled due to contamination, and now it’s claiming that this new PURE series is totally different from its old product. That means it has months of dosing experience. There are many other recommendations here that make no sense, like not injecting into a damaged tendon because that causes too much of an inflammatory response. Or that you should be injecting this stuff into intervertebral discs at 15 million cells per level. Here they claim to have clinical trials that show that a 14 million cell number is appropriate for the disc. So where is this citation? Not in this document. I searched the US National Library of Medicine for “intervertebral disc umbilical cord.” The only clinical study I found used a completely different cell type (isolated and culture-expanded umbilical cord stem cells) in two patients (hardly a clinical trial) at 10 million/ml. Meaning, the nucleated cell count that the Liveyon product reports has NOTHING to do with the isolated and culture-expanded cell number reported in this clinical case report.
- Is 60%–70% Cell Viability After Thawing Good? The FAQ notes that viability in the clinic can range from 50–70%. This FAQ doesn’t say much else about why this is good or bad, but to learn why those numbers are awful see my video below:
However, the FAQ beneath this question tries to claim that the Liveyon cells still function in the body. However, Liveyon has never satisfied the FACT guidelines to prove this is the case (see my video above, earlier in this piece).
- Are Some Growth Factors More Concentrated in PRP Than Umbilical Cord Cells? This FAQ tries to make the assertion that while platelets have higher growth factor levels, Liveyon umbilical cord cells survive for weeks and months in the body so they will eventually pump out more. Again, we have no data that the cells in this Liveyon product survive at all, and the data published by my research lab and that of Lisa Fortier’s at Cornell clearly show that this type of product doesn’t contain cells that would survive to pump out growth factors. Hence, the growth factors in the mix at the time of injection are all you’re likely to get. We do know that whole platelets continue to pump out growth factors for 7–10 days.
- Does BMAC have a higher concentration of IL-RA than Umbilical Cord Cells? The FAQ makes the assertion that there are higher levels of an anti-inflammatory protein most commonly known as IRAP in Liveyon than in the bone marrow concentrate of older patients. Again, no citation is given. This paper shows that IRAP levels in bone marrow samples were 13,432 pg/ml in bone marrow. The data for Liveyon shows a similar value but was obtained by breaking open all of the cells (a lysate); whereas, the bone marrow study measured it in the serum (which would artificially increase the amount in the Liveyon product). The mean age of these bone marrow patients? 48.2 years. Meaning, they were mostly middle-aged or older.
Circling Back After My Review
A friend this week had some words of wisdom for what we see in the amniotic and umbilical cord birth tissues industry right now. He relayed that it only takes a few minutes for scammers from other industries to make claims that have no basis in this one. The problem? It takes hours and hours of my time to debunk these claims.
In summary, this FAQ from Liveyon is generally not worth the paper it’s printed on or the photons used to display it on your computer or phone. I have no idea who wrote this thing, but they hopefully were not a medical doctor nor a Ph.D. However, I have reviewed similar documents from the company that were also full of misinformation.
The upshot? As you can see, the Liveyon PURE series FAQ is not accurate in many areas and downright misleading in others. Why take the time to do this? Because it seems like outside of a few scientists, like Lisa Fortier at Cornell, there aren’t that many people willing to devote the time and energy to call these companies out on the fiction they are creating. More importantly, given the poor state of physician education in this area, most doctors get their education from sales reps, which is truly the blind leading the blind. They then pass that fiction on to patients, which is how a real mess begins. I hope the FDA continues to crack down in this industry, as it’s destroying the credibility of the whole field of orthobiologics.