Dissecting Ads for Regenerative Therapies: The Selling of Amniotic Fluid Products – Part Two

Value of Exosomes in Amniotic Fluid Products

The focus of the previous post was on reviewing statements I found puzzling that appeared in an ad for an amniotic fluid product offered for sale by Apex Biologix. I explained that amniotic fluid without viable cells or micronized tissue is considered by the FDA to be excluded from 21 CFR 1271, much like blood, blood products and bone marrow aspirate. However, some of the Apex ad’s statements seemed to me to give an overly rosy view of amniotic fluid-derived products, ignoring completely the fact that there is no clinical efficacy data published on amniotic fluid that I could find. I will explore two points in this post concerning the presence of meconium in amniotic fluid and the promotional language Apex used in the ad concerning the latest, but greatest regenerative therapeutic agent: exosomes.

For those who aren’t familiar with meconium, or who have blotted out memories of meconium from the time of their welcoming home a new borne child, meconium is fetal fecal matter. When I have commented previously about this waste product and its presence in amniotic fluid, I have been reminded that it is sterile fetal fecal matter. But I am not sure the fecal material being sterile changes anything, since meconium-stained amniotic fluid is fairly common, having been reported to occur in more than 9% of pregnancies. Which leads me to consider a couple of related questions:

1) How does a collector of amniotic fluid know when the fluid they are collecting is not contaminated by meconium?; and

2) If the meconium contamination is high the amniotic fluid will have a dark color, but how do the manufacturers of amniotic fluid products try to minimize meconium contamination?

Apex didn’t mention the level of meconium in their amniotic fluid product and they left it off the list of biochemicals found in amniotic fluid in their ad.

Obviously, the presence of meconium, and the proteins and other biomolecules that comprise it, clearly isn’t a selling point for getting an injection of amniotic fluid for whatever ails you. How would you respond if your physician were to ask if you wanted to get treated with a preparation that had fetal fecal matter in it? My point exactly. So, it isn’t surprising that hawkers of amniotic fluid don’t really address the issue of the role meconium might play in the therapeutic potential of these seemingly magical products. But, as they say, meconium happens.

On the other hand, the Apex folks couldn’t be more up front about the presence of exosomes (a subgroup of extracellular vesicles) in their amniotic fluid product. They tell us with what I sensed was almost breathless wonderment that their product contained exosomes and they have a report to prove it! For the un-initiated, exosomes are little (and I do mean little, being in the range of 30-100 nm in diameter) bundles of goodness, or so everyone is supposed to think. These particles are generated within cells due to inward budding, with subsequent release into the extracellular space after fusing with the cell’s plasma membrane. Exosomes have been found to contain proteins, mRNA, miRNA and other biomolecules, all of which are thought to play an important role in cell-to-cell communication.

In my opinion, the Apex folks committed a few sins with their effusive extolling of the virtues of exosomes in amniotic fluid. Here are the two statements they made on exosomes from their ad:

“Amniotic fluid is shown to naturally contain a significant amount of exosomes”

“Exosomes are small cargo-carrying vesicles that contain proteins and RNA, and contribute to cell signaling functions that can lead to tissue repair and the transfer of proteins.”

In the first place, Apex and all of their competitors who hawk amniotic fluid products, assume that regardless of the contents of exosomes found in amniotic fluid, their impact is going to be beneficial. There is absolutely no evidence to support this speculation. It is true, as the second Apex statement indicates, that exosomes carry “…proteins and RNA…”, but they don’t cite a single paper to show that amniotic fluid-derived exosomes have any value in treating orthopedic pathologies. The other point to keep in mind, is that exosomes are found not just in amniotic fluid, but are a natural part of cellular physiology for almost every cell in our bodies, so stem cells or placental-derived cells don’t have a monopoly on exosome production.

From all that I have read, exosomes carry payloads that definitely are able to influence targeted cells. And I don’t doubt for a minute that exosomes in amniotic fluid will carry biological components that will have an impact via cell signaling functions, as indicated in the Apex statement. But what might be the message written in the nucleotides of the RNA contained within exosomes from pregnant women? I suspect the exosomes are trying to send the message that the woman is going to give birth, which certainly would be relevant since amniotic fluid is collected from a woman just prior to her delivery. Which leaves me more than a little perplexed, since I am not sure how exosomes announcing that “you are about to give birth” will be carrying any proteins or RNA bits and pieces useful in treating orthopedic pathologies.

I just don’t see too many parallels between giving birth and tearing an ACL or meniscus, other than pain. I haven’t given birth, but my wife has, and she definitely didn’t hold back her feelings during that process. I have torn a medial meniscus, which hurt like a son-of-a-gun, but given my wife’s experience, my pain definitely didn’t rise to the same level of pain as her giving birth. So, perhaps the hawkers of exosome-laden amniotic fluid are hoping that there are enough exosomes that might provide some therapeutic benefit for treating pain, even if it is orthopedic in nature. Apex mentions that their amniotic fluid product has “…a significant amount of exosomes”. But the obvious question Apex doesn’t answer is what is a significant number of exosomes? I haven’t seen any clinical data showing a correlation of the number of exosomes present in amniotic fluid with a beneficial outcome from treating any orthopedic condition with amniotic fluid in humans.

Despite the foregoing, I applaud companies like Apex for keeping to the straight and narrow with respect to hawking amniotic fluid products—selling products that are declared to be cell-free and that don’t contain micronized tissue, both no-nos with the FDA. But that they have latched on to the presence of exosomes, when so little is known about what exosomes can do as a regenerative therapy, suggests that there isn’t much else amniotic fluid has going for it.

In the next post, I will take up a broader consideration of what the research literature has revealed about exosomes over the past 20 years following their discovery, along with some speculation on my part about the regulatory implications of donor-derived exosomes, whether from amniotic or other biological fluids.

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