Several weeks ago I blogged on a trend racing through the stem cell community-doctors using GUNA “cytokines” to help stem cell procedures. I found serious scientific issues with the concept and I promised that our lab would do it’s own homework on the topic. The results are in and they’re not pretty.
First, as I have said before, what the doctors using this product have likely picked up on is the fact that there are hundreds of scientific papers showing experiments where certain growth factors can stimulate or move stem cells toward one type of cell or another. To review, a growth factor (GF) is a chemical used by the body to stimulate growth of something. GFs can be purchased at scientific supply houses and used in ultra precise doses in culture to stimulate stem cells. However, none are approved for human use (other than Human Growth Hormone and it’s analogues). I first became aware that a company was claiming to produce a wide array of biologically active GFs for use in humans through seeing the company’s booths at medical conferences. The company sells bottles labeled with common growth factor names like TGF-beta and FGF.
I also began seeing orthopedic stem cell web-sites advertising like this:
“Up until now these specific factors were extremely expensive and sometimes had significant side effects. Previously, it was almost impossible to obtain these growth factors. They are now available and are OK with the FDA and are extremely safe if used properly. The trick is to learn to use them in the proper dosage regimen and combination. Luckily the company we are dealing with is a company that has staff who are the expert’s expert in the field of cytokine medicine. In simplistic terms what we have now achieved is the ability to significantly affect the joints or tendons we are working upon in a very positive way. These factors dramatically increase the efficacy of the stem cells to accomplish repair.”
My last review of using GUNA cytokines to help stem cells showed serious issues with the concept. First, they had no advertised dose, despite the fact that ultra precise dosing is what using GF’s is all about. Second, when I did find a dose range listed in a study that used the product, it was well below any commonly used dose that could likely help stem cells. Third, the GFs are sold in water with a high alcohol content and not guaranteed to be sterile, which likely degrades the cytokines and makes them impossible to inject or test directly with cells (the alcohol levels will kill stem cells dead and the chance of bacteria in the bottle is an issue).
Unlike almost all other stem cell clinics and doctors who use stem cells, we test all claims in our own lab before deciding to use a product. This was no different. However, the high alcohol content guaranteed that these products would kill cells, so we couldn’t test them directly with cells. This left performing an ELISA assay to see if there were any reasonable detectable levels of the GF’s in the bottle. ELISA (enzyme-linked immunosorbent assay) is a technology that uses antibodies and enzymes to very accurately measure how much of something is in a solution. The results? For all practical purposes, there were no GFs detected in Guna Cytokines in our tests.
First, we purchased several bottles of GFs from Guna, focusing on two that would be game changers with stem cells-TGF-beta and FGF. These two GFs are both well known to help stem cells grow. They are often used in the nanogram dose range (one billionth of a gram). We tested the Guna bottles of each down to the picogram range (one thousandth of a nanogram). The graph above shows the ELISA results. On the left shows the reference ranges we used (0-2,000 picograms per ml). The second to the last bar on the right shows how much TGF-beta is in just 30% alcohol off our lab shelf (i.e. none). The bar on the far right shows how much is in the Guna TGF-beta bottle-none.
So there are no detectable levels of TGF-beta (or FGF-see below) in a Guna bottle down to levels well below those commonly used with stem cells (1 picogram or one trillionth of a gram). I brought up in my last post on this topic that maybe there were femtograms of the GF in the bottle (one thousandth of a picogram). However, we couldn’t find a commercially available assay that goes down that low. In addition, there is very little research to clearly show that this super duper low level of GF would help stem cells. Hence even if we could get this extremely low dose of GFs to cells (an extremely big if based on my discussion above), we would have little data on which to base it’s use with stem cells.
The upshot? As an example of the “stem cell wild west”, we have doctors buying these GFs and using them in patients without any knowledge that what they’re buying and using will impact stem cells in any way-based solely on what a sales rep tells them. As you can see above, we have doctors prominently displaying on their web-sites the miracle of using “cytokines”, without any confirmation on their part that there is enough in the bottle to help stem cells. In the end, based on what we’ve found, if you have a doctor who wants to use “cytokines” on your knee, hip, or shoulder because it will help stem cells, you just learned an important lesson about the physician-i.e. what that doctor is offering hasn’t been rigorously thought through…