If you read this blog, you know I get sent info from colleagues all the time. This morning I’d like to dig into a press release by R3, a company that sells and markets amniotic and cord tissue as “stem cell” treatments. The focus of this release is treating the problems associated with stroke, and it links to research purporting to show that this therapy is safe and effective. Regrettably, the research the press release cites has little to do with the therapy R3 is offering. Let me explain.
Claims That Amniotic and Umbilical Cord Products Contain Stem Cells
If you read this blog regularly, you know that we and others have extensively studied commercially available birth-tissue products, like amniotic fluid and membrane and cord blood, and found NO viable and functional stem cells. See my video below for more info:
In addition, these are regulated to be dead-tissue products in a 45-minute, quickie registration on a website and NOT FDA-approved products. For more info, see my video below:
Who Is R3 Stem Cell?
I first noticed R3 when they were advertising on Google and selling vials of what they claimed were amniotic stem cells. I knew based on our lab research that this was unlikely to be true, and knowing the regulations involved in an FDA 351 live-cell, drug claim using a dead-cell 361 tissue registration, I was surprised. To learn more about this issue, see my video below:
So R3 is a birth tissues vendor claiming that its products have live stem cells. While it’s unlikely that this is accurate, even if it were, its products would need an FDA cell-drug approval (351) requiring years of clinical trials and not the quickie online registration they currently have (361).
The Press Release
I was sent this press release this morning by a healthcare colleague:
“R3 Stem Cell Now Offering Regenerative Therapy for Post Stroke Patients”
Hmmmm…I read further and here’s what I found:
“Stem cell therapy for stroke is showing to be effective for helping patients recover well after the eighteen month time frame. Excellent studies such as the recent one out of Stanford showed that patients achieved excellent improvements in motor function even years afterwards.
In addition, the stem cell therapies for stroke have been shown to be safe for patients, with no significant complications.”
Wow! Knowing that the FDA is on the warpath for physicians and companies treating incurable neurologic diseases, like stroke, this seemed like a very bold move indeed.
Does a Stem Cell=a Stem Cell=a Stem Cell?
There are many different types of stem cells. The biggest differentiation you may have heard about is between embryonic and adult. Embryonic stem cells come from embryos, and adult stem cells come from everything else, including adults. However, there are much finer distinctions than these broad categories.
The most commonly published adult stem cell type is a mesenchymal stem cell, or an MSC. This is usually derived from bone marrow, but it also can be derived from fat or other tissues. This is a great “all around” stem cell for multiple repair purposes. In particular, as my video shows below, it’s very important to note for this review that the research says that MSCs are generally RARE in umbilical cord blood:
In fact, they can only be isolated in a very low percentage of umbilical cords. Hence, even if you used fresh umbilical cords to harvest the blood, you would have a significant number of MSCs in only about 1 to 2 in 10 of these cords. This means that any commercially available cord blood product in the U.S. is very unlikely to have many MSCs. In addition, it’s also very unlikely to have live and functional stem cells at all.
Think of all of this like an antibiotic. You may know that different antibiotics kill different bugs, so choosing the right one is necessary to get rid of that cough. Hence, in the same way, choosing the right stem cell type is critical. In addition, a research study that used antibiotic A to treat bug B can’t be compared to one that used antibiotic C to treat bug B. Or a study that rubbed antibiotic A on the skin can’t be compared to one that administered it IV.
R3’s Research Page
By clicking a link in the press release, I landed on a research page on this topic that lives on the R3 website. Basically, the page claims we have copious research that using stem cells to treat stroke is safe and effective.
The RC page cites a few different studies. Here are the citations:
- Bang et al, which is a tiny randomized controlled trial involving 5 patients who got IV infusion of autologous culture-expanded mesenchymal stem cells (MSCs).
- Chen et al, which is a meta-analysis of 16 studies. These used neural stem cells (NSC), bone marrow mesenchymal stem cells (MSC), and umbilical cord mesenchymal stem cells (UC-MSC). Most of these used bone marrow MSCs (12), and only one used umbilical cord MSCs.
- Lemmens et al. This is just a review of the basic science of why this would work without much clinical data that it does work.
- Martino et al. This is another review article similar to Chen et al, with the studies largely using either culture-expanded bone marrow MSCs or bone marrow concentrate. The results of these studies are sometimes positive and sometimes negative.
The Research Done by Others
R3 uses commercially available cord blood. As you can see above, that would be a problem as only one study reviewed in the citations used umbilical cord blood. However, that study used a very different product than R3 utilizes.
That study was done by Shen, and near as I can tell (the article appears to be in Chinese as the reviewers stated that most were not in English), this study used isolated and culture-expanded umbilical cord MSCs. In addition, they injected these into the carotid artery of patients who had just had a stroke (meaning acute). The dose? One billion MSCs.
So given that we only have one study quoted by R3 that used MSCs from umbilical cords by injecting these into the carotid artery to gain access to the brain, how is R3 applying the cells? Meaning for the results of this tiny study of 32 patients to apply (only 16 of whom got the treatment), R3 would have to be using the same exact cell type and applying it in the same exact way. R3 gives a small amount of its cord blood intravenously (IV) and intranasally (up the nose). So R3 is using a VERY different delivery route, which means the results of this small study generally do not apply to its treatment method.
In addition, as shown above, based on our testing and those done by others, it’s very unlikely that R3’s product has any living and functional stem cells. Cord blood is also very MSC poor. Hence, the authors of the Chinese study used a completely different technique to get MSCs out of cord blood. R3 is limited to use simple methods to concentrate cells per the FDA. The Chinese team used methods illegal in the U.S. that involved isolating and culturing the cells to get MUCH greater cell numbers. In fact, they delivered a billion MSCs through the carotid artery. Given the limitations of the processing for cord blood products in the U.S., it would be close to impossible to be able to get a billion live and functional MSCs into the 2ml volume of cord blood that R3 claims it uses.
But Wait, What About a Stanford Stroke Study?
The press release also links to a Standford study, but this study used, again, completely different cells delivered in a very different way. Here, the authors used bone marrow MSCs that had been genetically modified. They then drilled a hole into the patient’s brain and dumped the cells directly into the area. This study is vastly different from the treatment being performed by R3.
Summarizing the Research
The R3 treatment uses commercially available cord blood products that are not FDA approved but are simply registered through a 45-minute form on a website. These are regulated as nonviable tissue (i.e., a dead cell product). Independent tests of a commercially available cord blood product claiming that it contained millions of variable and functional MSCs found no living cells that survived for more than a few hours. In addition, the published research shows that it would be very unlikely to find MSCs in cord blood at all, or they would be very rare. R3 then references studies that used mostly isolated and culture-expanded MSCs (illegal here in the US) or the patient’s own bone marrow and not US commercially available cord blood products. The one study it referenced that used cord blood used a completely different cell processing process and cell type than what would be found in US cord blood products.
The delivery route is also an issue because R3 is using intravenous and intranasal delivery. However, the only study it referenced that could possibly apply to R3’s protocol injected the cells into the carotid artery. The Stanford study that was directly cited used a totally different cell type and injected those directly into the brain using surgery.
In summary, R3 has quoted a bunch of research that has very little in common with the treatment it’s offering. As you can see, this takes some understanding of what’s going on, so the average reader will believe erroneously that R3 is using the same treatment that has shown to be safe and effective in these small trials.
Where Is R3’s Own Research?
I can find no original research published by R3 on this topic. Meaning, since these studies that it cites don’t readily apply to what’s being done, there should be research that R3 has performed and published on the technique it uses. In addition, there should be online and transparent outcome information on all treatments that have been performed. This is also not available.
What Product Tests Are Needed to Convince Me as an Expert?
There is a simple series of tests described by the Foundation for the Accreditation of Cellular Therapy (FACT) that would define if R3’s products had any viable and functional mesenchymal stem cells. I describe that testing below:
Basically, R3 would need to have a third party do ALL of these tests to confirm the presence and number of MSCs in its products.
Will I Send My Patients?
We only treat orthopedic problems. Hence, as a physician, if I get a call from a patient who asks where he or she can find a good stroke stem cell therapy for their loved one, I need to find a place to recommend or state that nothing exists right now. Given the research I reviewed today that R3 cites, I can’t recommend this therapy to that patient who needs a referral.
The upshot? As you can see, what R3 says it’s doing bears little resemblance to the research performed by others that it cites as support for its therapy. This is not unique to R3, but is, in fact, a feature of most online offerings of stem cells. When research is quoted, it often has nothing to do with the therapy being offered. So, again, as I always say, buyer beware!