Stem cell clinics, FDA, and giant, unapproved for-profit human experiments

When I started blogging in 2010 the stem cell arena was a very different place.

Back then the hot topic was the battle over the legality of federal funding of embryonic stem cell research. That battle is over, or at least in hibernation, with a 2013 federal court ruling allowing such funding to continue. The stem cell debate of today, which in its own way is just as fierce as the old one, is focused on how best to regulate the clinical translation and commercialization of innovative stem cell technologies.

The stakes in this new stem cell battle on the regulatory front are very high both for the stem cell field and for patients. Too little regulation could lead to harm to patients and damage to the stem cell field at a crucial juncture in its history, while too much regulation could stifle stem cell and regenerative medicine innovations.

Stem cell clinics should be better-regulated than a Starbucks

The goal of stem cell advocates, including myself, is to find a regulatory sweet spot where science-based, innovative stem cell medicine can advance expeditiously. On the other side we have largely physicians and lawyers along with some patients arguing for drastically-reduced regulation and acceleration of for-profit stem cell interventions to patients, even without concrete data supporting safety or efficacy.

The latter group is a key part of a rapidly-proliferating stem cell clinic industry in the US. It consists of for-profit stem cell clinics that collectively have already conducted stem cell transplants on potentially thousands of patients without federal regulatory approval. These clinics have in effect thrown down the gauntlet to the US Food and Drug Administration (FDA) with their use of non-FDA approved stem cell products on patients. 

Role and authority of the FDA

The FDA is the regulatory body legally empowered to regulate biologic products and hence stem cells in the US. However, the clinics generally argue that they and their stem cell products should not be regulated by the FDA because they believe that the products are not drugs and they as the physicians transplanting the stem cells are just conducting “the practice of medicine”. FDA guidance over the years has consistently conflicted with this view and indicated to the contrary that these clinics are generally producing a stem cell product that is a biological drug. Even so the clinics at this time do not have FDA approval to make and use stem cell biological drugs. Such approval can come in response to what is called an Investigational New Drug (IND) application. The clinics do not have IND approval from the FDA for their stem cell products or devices and do not have the licensing (called a Biological License Application or BLA) needed to produce and administer biological drug products such as certain types of stem cells. Collectively, for these reasons (absence of BLA and INDs), I define such clinics as “unlicensed” and their products as “unapproved” or “unproven”. Note that the physicians practicing at such clinics generally do have medical licenses from state medical boards, so they personally are licensed in that sense. These clinic physicians frequently further point out that doctors themselves can only be directly regulated by state medical boards and not by the FDA.

Where does the FDA get its authority to regulate stem cell products and clinics? The Federal Food, Drug, and Cosmetic (FDC) Act and the Public Health Service (PHS) Act give the FDA the legal authority and responsibility to regulate biologics including human stem cells. Therefore, barring a federal court specifically overturning a particular FDA decision, FDA regulations are essentially law when it comes to clinical use of stem cells in the US. The FDA is given certain authority over stem cell biological products and procedures more specifically under several regulations including “21 CFR Part 1271.10“, modified by “21 CFR 1271.15“, which details exceptions to its regulatory requirements. A key term to know before trying to decipher the verbiage in these regulations is “human cell and tissue products” or “HCT/Ps”, which basically means human biological products including human stem cells.

The state of the market

Both individual doctors doing stem cell transplants and chains of dozens of stem cell clinics have sprouted up from coast to coast in the US in the last few years. These clinics, collectively numbering more than 20 in the state of Texas alone and more than 100 across America, are administering stem cell transplants of one kind or another to growing numbers of patients each year, potentially generating millions of dollars in income, all without FDA approval. In doing so many of these clinics, even absent litigation against the FDA, are operationally challenging and undermining the authority of the agency by acting as medical providers using stem cell products without FDA approval or licensing. They are also a direct challenge to science-based medicine more generally. To put it more bluntly, I believe these clinics are in essence collectively doing a huge, unapproved human experiment for profit.

The FDA has issued a steady stream of regulatory guidances, supported in some cases by court decisions (e.g. US v. Regenerative Sciences Inc.), painting a clear picture that stem cell clinics in a general sense (as well as their products, devices, and procedures) are within its regulatory domain and their products can be defined as biological drugs. Furthermore, in 2012 and 2013 the FDA took numerous actions related to stem cell clinics such as warning letters issued to a number of clinics including the Texas stem cell clinic Celltex, which is well-known for having treated Governor Rick Perry.

Strangely the FDA took no regulatory action regarding stem cell clinics in 2014, at least none that is evident in the public domain, but the FDA did issue important new draft guidances related to stem cells (see herehere, and here) that I predict will be the basis for future action. One part of these guidances focuses on “minimal manipulation“, which is a key term in the stem cell clinical world and more broadly the world of biologics. If a biological product is defined as more than minimally manipulated it automatically leads that product to be defined as a biological drug subject to the full spectrum of drug regulatory oversight by the FDA. While stem cell clinics frequently argue that their products are less than minimally manipulated, it is becoming clearer that a large fraction of (but certainly not all) stem cell products sold by various clinics are likely to be viewed by the FDA as more than minimally manipulated.

The FDA and the stem cell therapy industry use numeric names for products that are minimally manipulated (361) or more than minimally manipulated (351), so these can be important to know as one navigates this arena. The for-profit stem cell clinics generally argue that their products are 361s, but I believe that FDA guidance indicates instead that a large number of these products are 351 biological drugs.

Treatment types, guidance and loopholes

It is also valuable at this point to talk about the different kinds of stem cell “treatments” sold by dubious clinics. The most common stem cell product transplanted into patients is something called stromal vascular fraction or SVF, which is a product manufactured from fat tissue. While various clinics use other stem cell products including cells isolated from bone marrow and other tissues (some of which may be 361s, while others are 351s), SVF is by far the most common stem cell product sold by clinics.

 Stromal vascular fraction, an extract of cleaned, centrifuged stem cells derived from body fat.

Amongst other things, the new draft FDA guidances explicitly single out SVF for attention and define it as a biological drug. This is particularly notable because many stem cell clinics have argued that SVF is not a drug and hence is not subject to drug-related FDA vetting. While many including myself have asserted in the past that SVF is almost certainly a drug and needs FDA approval before use, these new guidances from the FDA articulate, far more specifically and unambiguously than in the past, how SVF is by definition more than minimally manipulated and hence a drug (emphasis mine):

Example A-1: Adipose tissue is recovered by tumescent liposuction. The adipose tissue undergoes processing or manipulation (e.g., enzymatic digestion, mechanical disruption, etc.) to isolate cellular components, commonly referred to as stromal vascular fraction, which is considered a potential source of adipose-derived stromal/stem cells for clinical therapeutic uses. This processing breaks down and eliminates the structural components that function to provide cushioning and support, thereby altering the original relevant characteristics of the HCT/P relating to its utility for reconstruction, repair, or replacement. Therefore, based on the definition of minimal manipulation for structural tissue, this processing would generally be considered more than minimal manipulation.

Because of these new FDA guidances, I believe the fat stem cell clinic industry could be subject to future FDA action. However, the FDA is slow and cautious in how it proceeds with even what seem to be relatively straightforward regulatory actions that could even be viewed as neutral such as simply visiting a stem cell clinic to obtain information on its practices, products, devices, and such. It is important that the science-based medicine community advocate for appropriate, expeditious FDA action.

Another key term in the stem cell clinical arena is “homologous use“. When applied to an HCT/P product, it means that the clinical use of that product must be highly consistent with (i.e. homologous to) the properties of the original tissue from which the product was made; if it is not homologous, even if minimally manipulated it will automatically be considered a 351 drug product. An example of homologous use would be the transplant of hematopoietic stem cells to treat a hematopoietic disorder. In that case, a blood-related product is used to treat a blood-related disease.

An example of non-homologous use would be the transplant of SVF (again, a fat tissue derivative) as an intervention for a neurological disorder, as fat is not homologous to the nervous system. In this regard, it is important to point out that many stem cell clinics offer up their stem cell products (most often SVF) to “treat” a whole menu of human diseases manifesting in tissues that having nothing to do with fat or with the other tissues of origin of the various types of stem cells.

In an example given in the new draft FDA guidance in the section on homologous use, the agency points out that use of SVF to treat a bone or joint disease is non-homologous use (emphasis mine):

Example B-2: Adipose tissue is recovered and processed for use, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent, to treat bone and joint disease. Because adipose tissue does not perform this function in the donor, using HCT/Ps from adipose tissue to treat bone and joint disease is generally considered a non-homologous use.

Another way that clinics try to get around having their products defined as biological drugs is through a possible FDA exception called “same surgical procedure“. The idea here is that if a procedure involving biologics such as stem cells is done in an autologous manner (the patient is both donor and recipient) and is completed in a single surgical procedure, then the biological product in theory might not be defined as a biological drug. It might be exempt from that designation because such procedures may have relatively lower risks. Many stem cell clinics have made the assertion that because in some cases they use stem cells in same surgical procedures that it means that they are not subject to FDA regulation of their product as a drug even if the product is, for example, SVF. However, the reality appears to be that the “more than minimal manipulation” and “non-homologous use” definitions trump the same surgical procedure exemption, discussed further in one of the 2014 draft FDA guidances mentioned earlier. What this means is that if your product is more than minimally manipulated or it is used in a non-homologous manner (either of these is enough), it is still automatically defined as a biological drug even if you use it in a same-day surgical procedure.

Stem cell clinic chains

The point of these FDA biologics regulations is to protect patients. It is logical that products that are more than minimally manipulated or used in a non-homologous manner pose higher risks to patients. As a result there is an appropriately higher requirement for evidence to support the use of such products in human patients. It is therefore of substantial concern that so many stem cell clinics in the US and around the world are going ahead and using experimental stem cell drugs as the basis of for-profit interventions without evidence that such products are safe or effective.

The stem cell entities in the US that concern me the most are chains of stem cell franchising clinics. These are rapidly-growing chains of affiliated clinics selling mostly fat stem cell-based interventions without FDA approval or licensing. Two examples of such chains are Cell Surgical Network and Stem.md.

Cell Surgical Network

Cell Surgical Network is a Beverly Hills-based chain of upwards of 50 stem cell clinics around the US that share philosophies, institutional review boards (IRB), procedures, devices, and malpractice insurance. They offer up SVF-based interventions for a wide range of medical conditions. I interviewed the leaders of Cell Surgical Network, Drs. Elliot Lander and Mark Berman, on my own blog last year (see here and here) and then raised my concerns about their operations, including my view that their SVF product is likely more than minimally manipulated, that they use the product in what I view as a non-homologous manner, and that the device they use is not FDA-approved for this application. Their device is a column, which is a laboratory tool used to separate cells from the rest of the components of tissues, manufactured by a company called “Medikan”.

In response to my question regarding the possibility that the Cell Surgical Network SVF product is a 351 biological drug (and one for which they do not have FDA approval such as an IND to use it clinically), Cell Surgical Network responded in part by invoking the same-day surgical exemption, which again to my knowledge does not apply in this case with SVF:

We produce SVF (over 40 ingredients and can’t be characterized) in a surgical procedure (can’t be approved by the FDA – they’ve never approved a surgical procedure). If the FDA can’t approve a surgical procedure, why would we possibly request them to approve this procedure?

It is worth noting that although arguably the FDA cannot directly regulate doctors or surgical procedures, the FDA can and does regulate drug products, biologics production procedures and devices in a general sense, which largely challenges the Cell Surgical Network’s argument as well.

I also asked Cell Surgical Network about the issue of their arguably non-homologous use of SVF to treat diverse non-fat related conditions (see their menu here). I found their response to be rather creative, but one with which I disagree:

We do have many conditions that we are looking at and in choosing them we have attempted to exploit either the regenerative, immuno-modulatory, or anti-inflammatory properties of SVF. Although SVF is used in all of our protocols, our deployment techniques vary considerably. I think the term homologous has been used rather loosely and in the field of regenerative medicine, a new paradigm defies simplistic categorizations of cell types. After all, what type of tissue is an undifferentiated progenitor cell? Can it be homologous? Isn’t it potentially everything? For example, if it forms cartilage then could it have ever been anything other than a cartilage precursor? Our comfort zone is that we are surgeons performing a type of surgical tissue transfer procedure. There is no difference than when we replace a bladder with ileum or a coronary artery with a saphenous vein from an extremity. At the end of the day, the ability to use various tissues to treat human disease is within the realm of a surgeon’s domain.

In this line of argument then, would anything stem cell-related be considered “pan-homologous” to every other tissue and could never be used in a non-homologous manner? That seems like a rather radical notion and one not consistent with FDA guidance. Further, can a surgeon pretty much do anything they want? That seems to be a rather extreme idea too.

Still, despite these concerns, to my knowledge the FDA has so far never taken any action related to Cell Surgical Network. Therefore, a reasonable question to ask is why, if from my perspective the FDA would view Cell Surgical Network as likely being non-compliant in its use of stem cells, has the agency apparently done nothing about it? The frank answer is that no one except the FDA knows why or why not they take specific actions and they do publicly discuss specific situations.

Stem.md

Stem.md is a similar group of stem cell clinics, but one that sprouted up on the East Coast. Stem.md has dozens of clinics too, including some using SVF as well as other types of stem cell products. While the Stem.md website frequently has changed over the years, as recently as a year ago they made some rather bold claims for their stem cell transplants including the remarkable statement that they “provide a treatment for every condition”. Sounds like a panacea, right? They also at one point claimed their “advances” were FDA-approved, although they took down that claim when I pointed it out to them as being incorrect. Like some other stem cell clinics, Stem.md has made a big deal out of treating pro athletes, including in their case former Yankee Bartolo Colon, which might remind you of the recent case where stem cell clinics Stemedica and Novastem arguably could have benefited from a free stem cell intervention performed on hockey legend Gordie Howe as a public relations opportunity.

Some of the same nagging issues come up with Stem.md as with Cell Surgical Network, including potential non-homologous use and more-than-minimal manipulation. However, as with Cell Surgical Network, to my knowledge the FDA has not taken any regulatory action related to Stem.md.

While the recent FDA draft guidances are a step in the right direction of increased clarity, if the FDA takes no action, or waits years to enforce its finalized guidances, the end result is that the FDA is undermining its own authority and I believe putting patients at increased risk. In principle, in the absence of FDA action, stem cell clinics can effectively argue that if their practices did violate FDA regulations then the FDA should have done something about it by now. In the absence of regulatory action, there is always the possibility that the FDA could view the clinics’ use of stem cell products as compliant. I would also note that my views presented in this article, of course, do not necessarily reflect those of the FDA, and the stem cell clinics view FDA regulations quite differently.

The role of ClinicalTrials.gov

A relatively newer, but important issue related to stem cell clinics is the listing of their stem cell interventions on the official US government’s clinical trials website, ClinicalTrials.gov. I recently interviewed the Director of ClinicalTrials.gov, Dr. Deborah Zarin, to ask her about key issues including specific questions related to stem cell clinic listings. I was concerned to find out that ClinicalTrials.gov largely operates on the honor system in terms of deciding whether to list trials submitted to it for consideration. For example, there is neither specific vetting of US trials (keep in mind that ClinicalTrials.gov lists trials from all over the world) for FDA compliance nor a requirement that trials list specific IRB or other key information. Trials listed on the database can also be of a for-profit nature (i.e. patients are charged simply for participating in the trial before there is concrete evidence that the product or procedure in question is safe or effective) and based on the information in the trial listing, there is no straightforward way for patients to know that reality. I believe that this situation puts patients at added risk and also puts the valuable mission of ClinicalTrials.gov in jeopardy.

The end result of this situation is that many for-profit stem cell clinics have trials listed on ClinicalTrials.gov and some use that listing as a marketing tool. What kind of money is involved here? Cell Surgical Network has a clinical trial listed with a projected enrollment of 3,000 patients and hypothetically if the organization makes $5,000 profit per patient that would add up to $15 million, again before the SVF product in question is even known to be safe or effective for the particular condition in question and without FDA approval or licensing.

I believe that a number of changes are needed at ClinicalTrials.gov including a requirement that for-profit trials be labeled clearly as such near the top of their listing page, that the listing of a given trial on the site should be prohibited from being used as a marketing tool by the entity responsible for the trial, and that the ClinicalTrial.gov team vet trials located in the US for FDA compliance and as needed consult with the FDA on this matter.

If you feel likewise, this is one case where you can easily take positive action during a specific window of time. ClinicalTrials.gov has issued a Notice of Proposed Rule Making (NPRM), detailed in a very recent open access New England Journal of Medicine article by Dr. Zarin. Comments on proposed changes including suggestions such as mine can be submitted in response to this NRPM, but only until February 19th. I encourage you to submit comments and I have dug through the websites to find this direct link that allows you to do so quickly and easily.

Conclusion

The overall bottom line with most stem cell clinics in the US is that collectively they could be viewed as conducting a huge, unapproved and for-profit stem cell experiment of a sort, on thousands of vulnerable patients who are often desperately looking for hope. At the very least these patients are spending money that they can ill afford to lose on stem cell transplants that probably do not help them. It is also quite possible that some of these patients are being harmed. Stem cells do not always do what we might hope and their power to potentially help patients is equaled by their potential to do harm, especially when not backed up by rigorous science and physician training. For example, fat stem cells are typically a heterogeneous mix of a variety of cell types with variable multipotency – meaning that they can not only form mature fat tissue, but also potentially blood vessels, bone, cartilage, or others. The growth of an undesired tissue in the wrong place could be a major adverse outcome. There is evidence of potential for patient harm including growth of bone in an eye and nose tissue in a spine from stem cell treatments that went awry. Some patients treated at stem cell clinics have died, including in the USGermany, and elsewhere.

More broadly in this new stem cell debate, the for-profit clinic argument for stem cell deregulation and weakening of the FDA’s role in regulating stem cell products is a direct challenge to our system of science-based medicine. Furthermore, while to those of us in the stem cell field it may often seem clear where we can place a dividing line between the dubious clinics and the ones who follow the rules, that line is at best fuzzy for the wider community (including patients). For this reason the ever-growing unapproved human stem cell experiment poses a grave risk to the legitimate stem cell field as well. Governmental entities such as the FDA and ClinicalTrials.gov perform important services in this arena, but can and should do better to reign in the “wild west” mentality of the stem cell clinic industry in America today. Advocates of science-based medicine have an opportunity to make a positive impact here as well via educational outreach, participation in the FDA guidance comment process, and advocacy for responsible clinical research.

Note: a version of this piece was first posted at Sciencebasedmedicine.org.

A Stem Cell Clash: Silva Comments on MBD3/NuRD Debate with Hanna

Researchers probing how to reprogram cells into powerful stem cells (induced pluripotent stem cells or IPSCs) and what the molecular mechanisms are behind this process have become entangled in a conflict.

Of course over the years scientists including stem cell scientists have had their share of disagreements and debates in the past including heated ones, but this reprogramming clash has taken it up a notch beyond past ones and has some unique elements to it.

For example, this scientific clash is unfolding largely in the public domain and involves post-publication review such as on PubPeer.

Looking under the “hood” of cells so to speak, their reprogramming involves a molecule called MBD3 and a corepressor complex called “NuRD” ( for more on NuRD see my review with my postdoc mentor Bob Eisenman on NuRD here in Cell). It seems that most everyone agrees that MBD3 and NuRD play some role in reprogramming.

However, what the exact roles of MBD3 and NuRD might be in this area are very unclear at this time and there are quite distinct views.

Jacob Hanna

On one side we have Jacob Hanna, a well-known stem cell scientist who was previously a postdoc in the lab of Rudy Jaenisch. Hanna (pictured at right) has had a number of very high profile papers including on induced pluripotency.

One major assertion from the Hanna Lab is that a repressive chromatin complex including MBD3 and NuRD proteins is inhibitory for pluripotency (e.g. in their Rais et al. paper that I discussed on this blog when it came out in 2013). I also had a chance hear Hanna talk at the 2013 Till & McCulloch meeting, where I asked him some questions from the audience (see here).

On the other side we have José Silva, another top stem cell investigator. Silva did his post-doctoral work in the lab of Austin Smith. Of course Jaenisch and Smith are two of the top scholars in the stem cell field. The Silva lab has published a Cell Stem Cell paper coming to pretty much the opposite conclusion of Hanna.

Jose SilvaThis stem cell conundrum has been the subject of vigorous discussion on PubPeer. Now this MBD3 disagreement has also spilled over to bioRxiv where further back and forth is ongoing. On Silva’s side of the MBD3/NuRD fence are also well-known researchers Brian Hendrich and Paul Bertone.

In an effort to get to the bottom of this and build a bridge for constructive discussion, I have invited both Silva and Hanna to comment here on this situation.

Hanna has indicated that he would prefer to wait a month or so until additional work is published and then will provide comment. Stay tuned for that as my invitation to him stays open.

Silva has provided comments now, which are included verbatim below:

“Please find below the key elements (in no particular order) being discussed on the ongoing debate on MBD3/NuRD and reprogramming and my view on these:

1- Levels of Mbd3 expression and its relation to reprogramming.

Rais et al. evaluated the potential of Mbd3 depletion primarily in the Mbd3fl/- heterozygous background. Dr Hanna claimed that these cells express hypomorphic levels of Mbd3, corresponding to 20% that observed from wild type cells. Dr Hanna also claimed that these cells could reprogram with near 100% efficiency. However, our analysis of Dr Hanna’s data revealed that Mbd3fl/- cells express instead nearly wild type levels of Mbd3. This is also in line with the quantification of Mbd3 levels in Mbd3fl/- cells assessed in Dr Hendrich’s lab and mine. This evidence led us to question the effective depletion of Mbd3/NuRD function as having been a significant factor in the reported increase in reprogramming efficiency. (Please note that Dr Hanna’s Mbd3fl/- cells used in the Rais et al. study were generated by Dr Hendrich’s lab.)

2- Use of elevated copy number of Oct4-GFP reporter transgenes to assess ongoing reprogramming efficiency

The high copy number of randomly integrated Oct4-GFP reporter transgenes may lead to spurious GFP expression in non-reprogrammed cells.

3- Comparison of reprogramming efficiency to a control cell line harboring a deficient Oct4-GFP reporter transgene.

While Mbd3fl/- cells harbored an intact Oct4-GFP reporter known to be promiscuous for expression in a range of cell types, the control cells were transfected with an alternative Oct4-GFP reporter with much greater specificity for pluripotent cells. This finding indicates that key methodology was absent from the paper, and the comparison of reprogramming efficiency between cell lines representing compatible measurement conditions was potentially invalid.

4- Reproducibility of Dr Hanna’s claims. Rais et al. was regarded as a  landmark paper in stem cell biology and numerous labs around the world have tried to reproduce these results. Their attempts using independent systems have been unsuccessful. We do not dispute that Dr Hanna’s cells reprogram relatively efficiently. However, based on our own experimental work and on the detailed analysis led by Dr Bertone of genomic datasets published by Rais et al., we found no evidence to support the claim that depletion of Mbd3 leads to deterministic reprogramming.

José Silva

This is your brain on diapers: new mindbogglingly cool imaging trick

Expansion microscopy brain

Swollen brain cells – Scientists modified the superabsorbant diaper compound, polyacrylate, to magnify brain tissue. Courtesy of Boyden lab, MIT, Cambridge, MA. NIH

In what NIH describes as “outside-the-box” thinking, an MIT team led by Edward Boyden has found a way to use a diaper ingredient to transform microscopy including brain imaging.

This is cool stuff.

Boyden’s group found that the super-absorbent diaper compound sodium polyacrylate, can be used in a very novel way for microscopy.

For any who have ever wished for a more powerful microscope (and isn’t that everyone?), Boyden’s team thought of something pretty revolutionary. Instead of pushing the microscope beyond the limits of optical physics, Boyden uses the diaper compound to make his samples bigger and hence they looked bigger under the scope under the same magnification. You can see a lot more.

I wish I had thought of that.

Even with the almost 5-fold acrylate-based expansion the tissues retained its general structure, but was just far easier to see.

NIH quoted Boyden:

“Our results show that we can scan large chunks of brain tissue with nanoscale precision. We think this can be applied to a variety of tissues and help answer a lot of different questions in science and medicine,” said Dr. Boyden.

In the future, Dr. Boyden and his team plan to test ways to combine the technique with other visualization methods and use it to study diseases in human brain tissue.

You can see an example of swollen brain cells imaged by the team above from the NIH website. Also from the NIH piece:

“Expansion microscopy is a potential game changer,” said Walter Koroshetz, M.D., acting director of NIH’s National Institute of Neurological Disorders and Stroke. “This is the kind of outside- the-box technical innovation that expands the capability of microscopes widely used in the scientific community to explore the fine structure of the nervous system in health and disease.”

All those years changing my kids’ diapers, then going off to look at samples on scopes, and this never occurred to me.

Stemedica reply on Olbermann interview regarding Gordie Howe

The stem cell company Stemedica along with Mexican partner Novastem conducted a stem cell intervention on hockey legend Gordie Howe, who had suffered strokes in 2014. This situation has sparked a lot of discussion and media attention including a recent interview with Stemedica leadership on the Keith Olbermann show on ESPN.

For balance and fairness I invited Stemedica to comment on this situation and below I have posted their January 23 response verbatim:

“As part of ipscell.com’s coverage of Gordie Howe’s participation in a stem cell trial for stroke, we believe several key facts have been missed, and certain circumstances have been misrepresented. Thank you for allowing us to set the record straight.

* Gordie was an accepted participant in a government authorized clinical trial in Mexico. That clinical trial meets all of their government’s requirements including: IRB/Ethics Committee oversight of an approved clinical trial protocol and the conduct of clinical trials; adherence to inclusion/exclusion criteria of the protocol; signing an informed consent; reporting adverse events; and, collecting other clinical data as outlined in the protocol.

* Gordie Howe, (as his family reported to the media), was not eligible for enrollment in Stemedica’s US-based stroke clinical trial due to certain inclusion criteria. The family did apply for enrollment in the stroke trial at Novastem’s Clinica Santa Clarita where the inclusion criteria are different. Stemedica’s stroke trial in the U.S. has a six-month wait period post-stroke and the family was concerned that Gordie might not live for six more months. The fact that the wait time for participation is different between these two clinical trials was the determining factor the family used in choosing the Novastem clinical trial at Clinica Santa Clarita.

* As a participant of a clinical trial, Gordie Howe’s involvement in that trial was confidential. There was no effort by Stemedica or our Geographic Distribution Partner in Mexico, Novastem, to breach that confidentiality. It was Gordie’s family, under constant requests from media and fans to know more about Gordie’s health, that they, (the Gordie Howe family), made a public pronouncement. Since then, we have professionally responded to approaches from the media after receiving a request from the Howe family to do so.

* It’s important to note that not all stem cells are manufactured the same way. Therefore, different stem cells manufactured by different companies exhibit different properties. There is still an honest and open debate about what role autologous adult stem cells, allogeneic adult stem cells, iPS cells and, embryonic stem cells are going to play in developing new medications for the treatment of various conditions in the future. The efficacy of adult allogeneic stem cells – as is the case with all stem cells – can only be evaluated based on data collected through well run and government-approved clinical trials.

* As was the case in Keith Olbermann’s interview with Stemedica’s Vice Chair/CEO, Dr. Maynard Howe, on January 21, 2015, whenever Stemedica has an opportunity to interact with the media, we make best efforts with that audience to emphasize the need to be cautious about: treatments which are unregulated; use of stem cells of unknown origin; and/or, promises or guarantees of positive outcomes. We work diligently to adhere to all laws, professional practices, and ethical standards. We encourage patients, like Gordie Howe and his family, to demand documentation of the clinical trial’s compliance with these guidelines before committing to any investigational treatment or trial opportunity.

* While the correspondence between the FDA and a clinical trial sponsor is strictly confidential, including IND numbers, we do confirm that all clinical trials sponsored by Stemedica have FDA approval. These trials are listed on the governmental web site ClinicalTrials.gov under the following numbers:

STEM 101-M; NCT01297413 A Study of Allogeneic Mesenchymal Bone Marrow Cells in Subjects With Ischemic Stroke.

STEM 102-M; NCT01771679 Safety Study of Bone Marrow Derived Stem Cells on Patients With Cutaneous Photoaging.

STEM 103-M-STEMI; NCT01770613 A Study of Allogeneic Mesenchymal Bone Marrow Cells in Subjects With ST Segment Elevation Myocardial Infarction (STEMI)

STEM 104-M; NCT02123706 A Phase IIa, Single-blind, Placebo-controlled, Crossover, Multi-center, Randomized Study to Assess the Safety, Tolerability, and Preliminary Efficacy of a Single Intravenous Dose of Ischemia-tolerant Allogeneic Mesenchymal Bone Marrow Cells to Subjects With Heart Failure of Non-ischemic Etiology.

We, too, wish Gordie Howe the best of health in the future. We trust that Gordie’s participation in Novastem’s stroke study at Clinica Santa Clarita fulfills the time-honored purpose of clinical trials.

Thank You,

Stemedica Cell Technologies, Inc.”

TGIF: Biomedical weekend reading includes some cool papers

I’m working on an R01, but I still try to find time to read a wide variety of papers. Below are the ones I’m hoping to get to this weekend.

Less Myc, longer “health span” Cell paper from Sedivy Lab.

ESC Histone H3.3 nucleosomal functions Epigenetics & Chromatin paper from Keji Zhao Lab.

Human PGC specification Cell paper from Jacob Hanna Lab.

SETDB1 & hnRNP K tango to silence ERVs in ESCs PLOS Genetics paper from Matt Lorincz Lab.

Novel antibiotic isolated from dirt Nature paper from Kim Lewis Lab.