In the previous post, I had begun a review of the distinctions between the potential utility of an IV infusion of a patient’s bone marrow concentrate and the utter futility of using amniotic fluid products currently on the market to treat anything, whether by IV or site-specific injection. One of the issues I commented on in the previous post was the poor recovery of viable cells in four vials of amniotic product I had been given by curious physicians. I will continue to contrast BMC therapy with amniotic fluid product use in this post.
It has been reported (Dziadosz, et al., 2016) that viability of nucleated cells present in amniocentesis samples ranged from 60-90%. If cell viability in amniotic fluid freshly obtained from the mom isn’t 100%, it isn’t surprising that viability could drop off substantially during the processing and packaging of the amniotic fluid, which means that the viabilities—nothing above 30% viable—I observed probably are accurate.
Another problem the hawkers of amniotic fluid products have is the absolute number of cells present in the products. Again, according to Dziadosz, et al., the range in cell number is from 20,000 to 30,000 cells per mL of amniotic fluid. That is the total number of cells, which Dziadosz et al. indicated included amniocytes, epithelioid, fibroblastic and progenitor cells. An estimate of the number of progenitor cells present in amniotic fluid was published by Loukogeorgakis and De Coppi (2016), who reported that typical amniotic fluid has about 1% or so progenitor cells, suggesting there are 200 to 300 progenitor cells present per mL of amniotic fluid, which sounds like a lot, but assumes that they are all alive once they are packaged up. Clearly, most of the MSCs aren’t viable, since in my personal experience I found only one CFU-F (a biomarker for MSCs) that grew out of four vials (four mL total) of amniotic product. In contrast, Dr. Hernigou has published that there can be anywhere from an average of 1,500 to close to 4,000 CFU-F per mL of BMC, and since the BMC is produced at point-of-care and typically used almost immediately, there shouldn’t be any issues with the viability of nucleated cells in the BMC.
Now we get to the part that separates a legitimate therapeutic material from a non-compliant therapeutic material. Amniotic fluid containing viable cells is considered to be an HCT/P and regulated by 21 CFR 1271, which means that amniotic fluid products are limited to being used in the donor (probably the neonate, but a case could be made for the mom) and first- and second-degree relatives of the neonate/mom. That is a pretty limited marketing opportunity. However, the hawking of amniotic fluid products with viable cells for use in unrelated recipients is not FDA compliant, without the product undergoing a Premarket Approval process (e.g, IND).
Of course, the reality is that amniotic fluid products might have only dead cells, in which case the FDA wouldn’t give a fig about them. But, the Federal Trade Commission (FTC) might take issue with a physician advertising “stem cell” containing amniotic fluid products for whatever ails their deceived patients. Throw in treatment via IV infusion and the FTC would have multiple angles to shut down clinics and physicians treating their patients with this magical fluid. In fact, the FTC did just shut down and levy fines against a physician and the two clinics he owned due to their making outrageous claims for therapeutic benefits of treatments with amniotic fluid products.
In contrast, the use of BMC to treat orthopedic conditions hasn’t been challenged by the FDA to my knowledge. I think one reason is that there is a long history of publications on the clinical outcomes of using BMC in orthopedic conditions, pioneered by Dr. Philippe Hernigou, demonstrating its safety and efficacy. Furthermore, use of BMC to treat orthopedic conditions comes closer to being a homologous use than anything being treated with amniotic fluid. Finally, my employer, Greyledge Technologies, has provided physicians with customized PRP and BMC preparations going back more than eight years, with one of our laboratories having been registered with and twice audited by the FDA for roughly the same period of time. If the FDA didn’t like the fact that Greyledge provides PRP and BMC to physicians for treating their patients presenting with orthopedic conditions, there has been plenty of time to let us know. And we just brought a new laboratory on-line last month.
So, there is no way the hawkers of amniotic fluid could seize on my review of the potential homologous use of autologous BMC to boost up degraded bone marrow depots via IV infusion to justify their influencing physicians to use amniotic fluid in the same manner. Dead cell-containing amniotic fluid won’t home to anything and live cell-containing products aren’t FDA-compliant. But these details don’t matter to the truly dedicated promoters of amniotic fluid, who have been touting IV therapy with amniotic fluid for several years, with no clinical evidence of efficacy and without any encouragement from me.
On the other hand, the recent FTC action mentioned above against a physician, and his clinics, for treating all sorts of pathologies with amniotic fluid products should be carefully reviewed by all physicians currently engaged in treating patients for anything with amniotic fluid products where there is a claim of “stem cell therapy”. I will explore the findings and orders of the court case brought by the FTC in the next series of posts.