A number of years ago I got an e-mail from a physician who had visited us in 2008 to see what we were doing with stem cells. It was around 2010 and he mentioned he was now using “cytokines” with his stem cell concoctions. I thought that was a bit odd, as I didn’t know of any FDA approved cytokines for human use. A few years ago I began to see a company pop up at medical conferences advertising that they had “cytokines” for sale. In addition, since then I have continued to hear from patients about physicians using “cytokines” from a company called GUNA. So what is this stuff and is it for real or just another stem cell scam?
First, cytokines are cell signaling molecules that act as a way for cells to talk to one another. They trigger receptors on a cell’s surface and are different from growth factors. Most of the GUNA “cytokines” that physicians would be interested in to help stem cells would actually be growth factors (GFs). GFs are very important in prompting stem cells to grow more copies of themselves or differentiate into certain tissues or even build new blood supply. GUNA lists many GFs-everything from TGF-beta, to FGF, to VEGF. This alphabet soup of GFs are all important for stem cells. So if GUNA really had these GFs for sale at a low price and somehow these flew under the regulatory radar as a homeopathic medicine, this would be a huge and important thing for physicians using stem cells to help patients.
Unlike most physicians who use stem cells, we actually have a research lab and have used many GFs in our lab experiments to improve the quality of what we can do for patients. What’s interesting is that the GFs we buy for research use only are quite unstable, so unlike their GUNA counterparts, they come in a powdered lyophilized form rather than a liquid. In contrast, GUNA ships it’s GFs in liquid with a very high alcohol content. My first concern with looking at the GUNA catalog of GFs was this difference. It’s very unlikely that GFs stored in water and alcohol would remain stable, meaning that they would quickly degrade. Second, GFs for research use only are insanely expensive, while the GUNA GFs are relatively cheap. This raised another red flag. In addition, research only GFs have very specific dose ranges, usually in nanogram to picogram doses (billionths to a trillionth of a gram). These doses are critically important when dealing with cells, as hundreds of studies show that cells can do quite different things when exposed to a nanogram dose versus a picogram dose of a GF. For example, one dose may stimulate more cells to divide, whereas another dose may shut cells down so that they don’t divide. GUNA lists no doses for it’s GFs at all! This is a humongous red flag! So what’s going on?
The GUNA web-site has many pages devoted to really fancy machines used for processing and I have to say that even I was impressed by some of the photos. The web-site states: “We are deeply convinced that our approach will be the basis of future medicine and we are certain there is a treasure of potentialities in the field of Low Dose Pharmacology which have not expressed themselves yet.” So what exactly is “low dose pharmacology”? Does that mean that they sell GFs in the dose range the body’s cells respond to like nanograms and picograms versus the massive doses used by most physicians (grams and milligrams)? As an example, if a picogram was represented by the height of a matchbook or USB thumb drive, a milligram would be represented by the height of 1,000 Empire State buildings stacked on on top of the other. Or are they referring to something else, since they list no doses on their bottles? The web-site says they conduct studies, so I next went to the U.S. Library of Medicine web-site and did find a few small studies. The first thing I found was that one of the studies noted that the dose range of GUNA cytokines are in the femtogram (FG) range. This is one thousandth of a picogram and one millionth of a nanogram. So will these ultra-low dose ranges impact stem cells?
One doesn’t need to look far to find research papers investigating how TGF-beta helps stem cells become cartilage, a topic near and dear to the heart of anyone with arthritis. The issue is that the normal dose used to get stem cells to go this direction is 10-50 nanograms. However, this is about 1-10,000,000 times the dose in a GUNA bottle. Meaning that if you wanted this dose, you would need a warehouse full of GUNA product. Having said that, I was able to find at least one paper that suggested that the FG range of TGF-beta could at least activate immune cells (not stem cells). So at least there’s some face validity to the concept that FG range GFs could be enough to tell some cells what to do. But how would we get GUNA cytokines to stem cells?
When our lab team first began to look into GUNA products they immediately discovered a very important issue when they found out that they ship in a water based solution with high alcohol levels. They are also not for injection, but for oral consumption. So if we add them to stem cells in culture to see if they work, the high alcohol content will kill the cells cells dead. If we (or anyone else) inject them with stem cells, we’ll get dead stem cells. In addition, since they aren’t guaranteed to be sterile, injecting them in a human would be unsafe. Finally, taking them orally would mean that the unstable GFs would be quickly chewed up by the digestive tract, meaning most or none of the GF would ever get to a knee.
Based on what we’ve been hearing from physicians who use these products, we’ve decided to test GUNA “cytokines” in our advanced lab. First we’ll perform ELISA assays and second we’ll determine if there is a way to avoid the product killing our stem cells in culture. Why? Because unlike other physicians using stem cells, we test everything in the lab to confirm a manufacturer’s claims before we use a product in patients. As a result, we frequently see that we’re unable to confirm in the lab what the sales rep told us.
The upshot? We’ll soon know if GUNA “cytokines” have any detectable levels of GFs. In the meantime, the GUNA story has some significant issues, not the least of which is that they have no dosing information (i.e. each bottle contains X femtograms of TGF-beta). In addition, even if the bottle does contain that amount, storing a GF in a water based alcohol solution should cause it to rapidly degrade. Finally, actually getting that GF at those specific levels to cells doesn’t seem possible based on the high alcohol content and the fact that the bottle isn’t manufactured to be sterile for injection. Finally, in their current form, no physician should be injecting GUNA “cytokines” into a patient!
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About the Author
Christopher J. Centeno, M.D. is an international expert and specialist in regenerative medicine and the clinical use of mesenchymal stem cells in orthopedics. He is board certified in physical medicine as well as rehabilitation and in pain management through The American Board of Physical Medicine and Rehabilitation.…