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.

60 thoughts on “Stem cell clinics, FDA, and giant, unapproved for-profit human experiments


  1. Great insight Mr Knoepfler, as always. I wasn’t aware of your interview with Dr Zarin,it was a great read. What is your take on the exceptions presented in the NPRM linked? For example, III.C.2 (b) says “A small number of applicable clinical trials may not be required by applicable law, regulation, and/or institutional policy to seek approval from a human subjects protection review board”. Does this mean humans will be available to experiment on without approval or support from an ethics committee?


    • I’m sorry to throw water on your thinking Mr. Knoepfler having great insights, but I disagree. I am living proof that Non-Embrionic Stem Cells work. I have had injections of my stem cells into my spine, four bad discs that kept me in serious pain for years and serious Claudication in my calves that kept me from walking more than a half a block without severe pain. The stem cell treatments I received have had the effect of rejuvenating my spine and my Claudication has been halted or reversed, as I can now walk 3 miles without pain.

      Anyone who denigrates this wonderful treatment is causing the Public serious harm. I am living proof it works, and have at least six friends who have benefited to a huge degree from this treatment. Not one has ever said that they hadn’t received what can be called magical results.

      Spencer A. Lehmann, RHU
      Palm Springs, CA.


      • I have also seen the effects of stem cells on complicated patients, and I also believe in the potential of stem cells, don’t get me wrong. Though I am also a believer of the scientific method, of good clinical practice and ethical research. There are certain steps to be taken before a biological product or drug is launched to the public, trusting its safety and efficacy, and these steps are standardized and harmonized. They may be inefficient or slow, and the methods to start a trial may be very long and expensive in time and resources, but they are the most secure and safe. There are currently various programs that target this slow clinical translation, like CIRM 2.0, and this is a product of continuous scientific research and advocacy. Althogh many patients may be “left behind” in the process of assuring its safety and efficacy, this is exactly what has happened in other trials and is a natural and necessary evil in the pursuit of research. For example, penicillin was discovered in 1897 and forgotten, re-discovered in 1928, and was approved for therapy until early 1940’s. Thirty years of patients dying of staph infections and syphilis when we already knew a way to stop microbial growth.


        • Hi Marcel,
          interesting post. I would like to know, where have you seen the effects of stem cells?
          What kind of therapy was used?
          Please let us know.


        • I think we should learn from this and not to let valuable treatments go by the wayside while people die unnecessarily. Over 40 years came and went before Penecillin was approved, this is the type of thing that should not happen again. Was that time lapse necessary?


      • Hi Spencer,
        I’m glad you are feeling so much better.
        I hope you won’t fault people for being at least somewhat skeptical when medical results are called magical and that all people always benefit.
        If Cell Surgical Network’s stem cell therapies truly work that powerfully and universally, it should be a piece of cake for the Drs. to prove it and publish the data. I hope they do.
        Thanks for commenting.
        Paul


        • No, Paul, I don’t, in fact understand that reaction. I’m not suggesting that all will benefit, many probably won’t.

          As I’m not a physician, but a layperson, my adjectives are going to be that of a layperson, and when I and my wife and friends who’ve undergone this treatment have all had good responses, it’s hard to find words to adequately explain how we feel about it.

          These physicians at Stem Cell Revolution won’t take every patient, and in fact won’t take anyone if they don’t feel comfortable that they can help.

          As to publishing papers, they do, have many times, and you may wish to contact them to find out where.

          I also know that they meet with many physicians around the country to explain the procedures and have found ways to make the procedures available to many who might not otherwise be able to access such care. You’ll need to talk to them for details. I’m sure that they’ll be happy to oblige.


  2. Paul- thanks so much for putting all of this information in one place. I’m sending on your post to people who ask me questions about stem cell clinics. Perhaps you can boil down this article to a few bite-sized messages for those, like me, who have the attention span of a hamster.

    An example could be: “A listing on clinicaltrials.gov does NOT mean that the trial is approved by the FDA.” and
    “The stem cells used by most clinics are drugs and the FDA must approve all drugs”.


  3. Nicely summarized, Dr. Knoepfler, and thank you for taking the time to put this together. I agree with Dr. Loring that distillation to specific take-home messages would also be useful. One thing to point out, though is that calling what is going on an experiment suggests that there is some kind of organized data collection and analysis going on that will eventually benefit patients. I am not sure whether what is going on can even really be called an experiment if they are basically just shooting patients full of uncharacterized cells without rigorously analyzing and publishing outcomes.


    • Yes, Jeane’s idea is a great one.
      I see what you mean, Shinsakan, as to “experiment”. What I meant by that is that the clinics use unproven products and procedures on patients, but you have a good point.


  4. I live in Palm Springs, Ca., and had stem cell procedure done in June of 2013 in Rancho Mirage, Ca. for a lifetime problem of a serious asthma problem and was cured by Dr. Elliot Lander and Dr. Mark Berman. I can now breathe deep breaths and not shallow breathing and will not be concerned with heart ailments as asthma ultimately leads to heart failure due to lack of oxygen. I have seen what great things can happen.

    A friend of mine had a stem cell procedure done on his heart by another doctor in 2005 in Bangkok, Thailand. Unfortunately, another doctor in Idaho the previous year, botched open heart surgery on my friend but because he had the good fortune to meet the ‘stem cell’ doctor in Thailand, he is now a healthy, living, walking testament to using your own stem cells. He was told he only had a few months to live by a famous cardiologist but is still here, 10 years later, in 2015; a living, breathing, healthy testament to this wonderful procedure of using your own body’s stem cells to live again; a true “fountain of youth”.

    Seeing and experiencing is believing. That’s why I have no problem in believing in Drs. Lander and Berman that the procedure would help me as well as other friends of mine for serious physical illnesses and my own wife, who can now walk without a cane for a stem cell procedure done on her crushed kneecaps, due to injuries she sustained in a horrific auto accident that was not her fault 3 years ago.

    We all are living proof that it does work.
    Edward Ortiz


    • This is the big difficulty to distinguish, which kind of therapy is good and which one is dangerous. If you take a look at PRP-therapy, this kind of stem cell therapy is now – after years, accepted.
      But for patients it is very difficult to judge.


    • Excellent response, Mr. Ortiz. Interesting as well, considering that I had years of pain due to four seriously deteriorating discs, had Claudication in my calves, and could only walk a half a block without severe pain.

      After seeing Drs. Lander and Berman, having stem cells injected in my spine and calves, can now walk 3 miles a day without any pain whatever, and have been given my life back by these two wonderful doctors.

      Not only does Non-Embryonic Stem Cell procedures work, they are the path to being able to gain one’s life back and live a healthy and fulfilling life.

      Anyone who questions the efficacy of this work simply isn’t doing justice to the public who benefits so greatly from this gift.

      I too, am living proof, as is my wife, who after suffering from arthritis in her knees, is back to playing Pickleball and living without pain.

      Spencer A. Lehmann, RHU


      • Could you please give us some more information about your therapy?, what kind of cells? how many? how cultivated? Where have you been treated?
        Thank you.


        • Richie, I’m happy to answer what I can: The process was performed at Dr. Elliot Lander’s Stem Cell Revolution office, and at Desert Medical Imaging. It consists of the taking of some of my adipose fat, converting that into pure stem cells, and then injecting the cells into the specific sites where they are needed. I don’t know how many cells were taken and then injected, but know that the number is high. I had injections into my spine while in the Desert Medical Imaging offices so that a Radiologist and physician schooled in the procedure was able to pinpoint the exact location to inject the cells.

          The cells injected into my calves for Claudication, were injected in Dr. Lander’s office, as well as the cells injected in my knees for arthritis.

          I was a downhill skier, raced, from my very early teens until my mid 40s, and had developed serious arthritis by the age of 19. It was diagnosed as Reiter’s Syndrome, whose main manifestation with me was arthritis. It didn’t help that I began lifting weights at age 12. As it grew worse I had to take Darvon or Percocet to alleviate the pain as I skied.

          When I grew older the arthritis grew far worse, and the pain in my spine (four seriously degenerated discs) was so severe that it took me several minutes to get out of bed in the mornings.

          After the stem cell injections, I was able to get out of bed with no pain, but most remarkable of all, while the pain from the claudication was so bad that I couldn’t walk more than a half a block without feeling like someone was running a hot knife down my calves, when I attended a national conference in Las Vegas at the Wynn Hotel just 3 weeks later, I found I could walk from the towers to the meeting rooms and around the strip, without any pain in my calves whatever. Only my hamstrings hurt from a lack of exercise for over three years.

          I don’t know how to privately let you contact me, but if you wish to do so, let me know, and I have written up a paper on the many areas in my body that have benefited from this treatment.

          Of possible real value, though I cannot explain the “how”, is that I have suffered Migraine Headaches all my life, from a very young age. Prior to the stem cell injections, I was experiencing 2 a week on average. Since those injections (June of 2012), I have not had a single migraine.

          So when anyone tells me that this is not an incredibly efficacious method of treating serious conditions, they are talking to the wrong guy.

          Incidentally, as a result of the seemingly miraculous recovery from these debilitating conditions as a result of the injections of Stem Cells (non-embryonic), a number of our friends and others we’ve met have flown to see Dr. Lander from other places in the country and literally every single one has told us that it has been the best thing that they’ve ever done for themselves. ALL have had wonderful results.

          You can find Dr. Lander at http://www.stemcellrevolution.com

          Please let me know if I can be of further help.


          • Hi Spencer,
            thank you very much for your information. I am glad to hear you are feeling so much better. It really sounds amazing. I think there are already good stem cell applications. It only seems to be difficult to distinguish between the serious and the non serious therapies.
            BTW Rafael Nadal seems to be healed by an stem cell therapy, too.

            Thank you very much.


  5. Dear Professor Knoepfler,
    would it be possible to make a list on your site about the different stem cell therapies?
    I think there are already accepted therapies to cure different eye-diseases, there is PRP and …. It would be a good help for patients, if you could judge the different therapies and everybody would know which one is approved and which one is dubious / unapproved.


  6. And just another question, you have written some weeks ago, that you will collect more information about the stem-cell-therapy of Rafael Nadal. This therapy seems to be successful. Rafael Nadal just reached the quarter-finals of the Australian Open, so you can say:

    a stem-cell-patient (maybe the first one) reached the quarter-finals of Melbourne.

    Before this Rafael had serious injuries and in my opinion it is an wonder, that he even could return to the center court.

    Have you got already some more information about his therapy?
    I think Rafa is the living evidence that this therapy is working. Of course Rafas treatment is not more than a case report, but a successful one.
    I believe his therapy is serious, because nobody knows exactly, where it was done, and no one uses Rafas therapy to advertise.
    If you can find more detailed information about Rafas therapy, please let us know.
    Thank you


  7. Paul, there is much in your fulsome exposition with which I agree and some which I see as being biased. If I get the time, I might respond in detail. For now, I just ask one question:

    How many clinical trials are not for profit?

    and my own view regarding that question is:

    Behind many (all?) clinical trials you will find people and organizations who are profiting. I shall denote your conception of for profit trials as “For Profit” and the bulk of other trials as being “for profit” and recognize the (theoretical?) possibility that some trials are “purely ultruistic”.

    Regardless of whether they are the subjects of “For Profit” or “for profit” or “purely ultruistic” trials, patients hope for a personal health advantage.

    You present dim view of those clinical trials which you call “For Profit”. But let me suggest that these “For Profit” trials are not so different from the “for profit” trials which you favour. They can both be poorly done.

    The biggest intrinsic difference is in who is doing the investing. I understand that “for profit” trials are funded by: big business, philanthropists and professional investors. These same groups may also partially fund “For Profit” trials. But what truly characterizes the funding of “For Profit” trials is that patients are also making a monetary investment.

    If your point is to make “For Profit” trials better, then I’ll back you to the end of the universe.

    Eliminating “For Profit” trials would be quite another matter. For every stem cell insider who sees “For Profit” as being either against their interests or ripping off patients, there will be a patient who feels empowered by the option to make such an ultruistic investment.


    • The norm is for pharma or therapy companies to pay for clinical trials. Of course companies want to make a profit from their drugs. What Paul meant was that clinical trial subjects generally do not pay out of their own pockets.


    • Hi Brian,
      You raise some good points and important issues.
      What is not for-profit when it comes to medicine?
      However, one thing I should have perhaps been clearer on is that a “for-profit clinical trial” as I mean it is one in which the sponsoring company makes money up-front in advance from patients just to allow the patients to be part of it.

      You don’t pay, you don’t get to participate at all. (which also raises ethical access issues)

      In addition, the company sponsoring such a trial makes profit regardless of whether the trial in question proves safety or efficacy or not for the particular product in question.

      Of course pharma companies and other biotech’s want their trials to eventually generate profit too and ideally big profit, but to my knowledge they are not generating profit simply from patients participating in the trial. For there to be profit in that context the drug in question has to actually have concrete evidence of safety and efficacy BEFORE the company can hope to make a profit.

      Make sense?

      I would argue that the “for profit” trials that generate profit regardless of outcome and do so even if the product in question is later proven to be junk are distinct in these important ways from traditional clinic trials where the profit only comes later and has a foundation of evidence. Of course even the latter can and have been shown to lead to negative patient outcomes, but I think the odds are far better.


      • @Admin: The argument of profit or non profit is one that is totally subjective, in my opinion. Years ago Insured the president of a Not-for-profit Health Care Service Contractor (I.e. the Blues). He made clear that there really is no such thing as a non-profit, as they all have to produce a profit or go out of business.

        As to the efficacy of paying up front, when dealing with a well known and vetted professional, as I did when having my stem cell treatments, the chances of success are the same whether paid up front or after the procedure.

        It can take as long as three months for stem cells to work their “magic”. In my case it took no more than a couple of days. In my wife’s case it took 2 months.

        We have both experienced miraculous results, which I’ve posted here already so won’t be redundant, but wanted to make clear that when some people, most perhaps, have to travel to other countries to receive the same or better treatment right here at home, I makes no sense to go to that expense.

        If you’re interested in contacting me to discuss this further I am happy to do so. As the admin, I assume that you have access to my email information.

        Respectfully,

        Spencer A. Lehmann, RHU


      • Paul, Yes, it certainly makes sense in the sense that the method of investment is different and the expectations of investors are different.

        I think that there are many models for the “clinical trials” business/charity that can be fair, equitable, and as safe as the conventional approach. BUT safety and fairness are things that really DO need to be worked on. Like you, I am NOT happy with the present state of affairs — although I may see the problems and solutions somewhat differently.

        Not so long ago I contributed to the crowd-funding of a book. Of course, I got a signed copy of the book and the author made a profit. (Or at least I hope he did). A patient paying to participate in a clinical trial might surely be thinking similarly?

        Patients paying to be part of a clinical trial might be doing so for the general good (and the chance of helping themselves). Similarly people donate to charitable organizations which then sponsor conventional development of medical treatments — and that seems to be OK, although even then I could point to ethical problems with the present state of affairs.

        I would say that a company that asks patients to pay for a clinical trial should also make the treatment it is developing “open source” — in the same sense as “open source computer code”. I get the impression that not all companies do that.

        If the “For Profit” company is successful in developing its treatment and they do not go “open source” then another fair option might be for paying patients to actually reap some of the profit (assuming the treatment proves useful).

        I see paying patients as potentially playing an important role for developing therapies that are expected to be unprofitable for the developer but would still prove most beneficial for patients and for the general practice of medicine.


  8. Fantastic post, Paul. Things have indeed changed since 2010. When I started working at the Stem Cell Network in 2008, our external communications plan didn’t even mention “stem cell tourism” or “unproven therapies” — the main concern with regard to public communications was a better understanding of embryonic stem cells. Now nearly every bit of public and media communications we do has an unproven therapies component. The issues, as always, are complex, nuanced, emotional and not well understood. Thanks for making things clearer.


  9. Paul, You certainly have stirred up a hornet’s nest with this one. I agree with you (as we have discussed privately) that there is a big difference between the so-called trials which force the patients to pay up front before it is known if there might be a benefit for the patient, and those trials being conducted after safety studies have been done and, as stated above, usually don’t charge the patients to participate.

    I have just learned about a trial in Egypt (at Al Azhar Univ.) for RP, using autologous bone marrow-derived stem cells, where the patients are asked to pay for the lab work to produce the cells. I have been trying to learn more about this study, but so far, the doctor heading up the study has not responded to my questions. If I learn more, I will pass along the information.

    Irv


    • Irv, I’m sorry to disagree, but I paid up front for my treatment, with no guarantee, and have had phenomenal success. As with any thing, it is a matter of vetting the provider, which I did, and anyone can.

      Drs. Elliot Lander and Mark Berman, at Stem Cell Revolution in Palm Desert, CA, have impeccable records, and not only have I had incredible success, but many of our friends have as well.

      It is unfortunate that this is not an approved method of medical and health care delivery. Imagine the wonders of paying a fraction of the cost of a hip replacement if stem cells can do the job and without any invasive surgery, that is both costly and whose efficacy is certainly not guaranteed.

      As a Health Insurance Agent and Professional for over 48 years, and one who has done battle with insurance companies to make sure my clients claims are paid, this kind of procedure should be available to all who need and want it.

      Sadly, our Pharmaceutical companies have far too much power and sway over the FDA and health care delivery. When they are taken out of the picture as regards that power, then the American Public will be able to see a great deal of improvement in their level of care. In my opinion, of course.

      ~ Spencer A. Lehmann, RHU


  10. Cell therapy drugs normally progress though 1) preclinical development, 2) Investigational New Drug (IND) application to FDA, 3) Clinical trials, and finally 4) FDA market approval through a Biologics License Application (BLA; New Drug Application [NDA] in the classical drug world).

    When I look up what an IND actually is, I find that it is simply an exemption from the prohibition of shipping unapproved drugs via interstate commerce (see below). Doesn’t that imply that intrastate use (i.e. drug production and administration at the same site: as in most SVF clinical applications) doesn’t need to have an IND? Doesn’t seem like there is a clear path for development/approval of “drugs” of this nature.

    Paul, If you have any insight into this it would be appreciated.

    http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/ucm176522.htm

    The IND is not an application for marketing approval. Rather, it is a request for an exemption from the Federal statute that prohibits an unapproved drug from being shipped in interstate commerce. Current Federal law requires that a drug be the subject of an approved marketing application before it is transported or distributed across state lines. Because a sponsor will probably want to ship the investigational drug to clinical investigators in many states, it must seek an exemption from that legal requirement. The IND is the means through which the sponsor technically obtains this exemption from the FDA; however, its main purpose is to detail the data that provide documentation that it is indeed reasonable to proceed with certain human trials with the drug.


    • Hi J,
      These are certainly challenging issues. Your points are definitely important.

      My impression, however, has been that the IND reach/requirement is not strictly limited to interstate commerce cases.

      For example, FDA essentially shut down Celltex (or at least its clinical operations in the US) via this warning letter:

      http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm323853.htm

      Key part for this discussion:

      “You are promoting the CellTex product in a manner that causes the product to be a drug under section 201(g) of the FDC Act [21 U.S.C. 321(g)] and a biological product as defined in section 351(i) of the PHS Act [42 U.S.C. 262(i)]. Please be advised that in order to lawfully market such a biological drug product, a valid biologics license must be in effect [21 U.S.C. 355(a); 42 U.S.C. 262(a)]. Such licenses are issued only after a showing of safety and efficacy for the product’s intended use. While in the development stage, for example, while being studied in a clinical investigation, such products may be used in humans only if the sponsor has an investigational new drug (IND) application in effect as specified by FDA regulations [21 U.S.C. 355(i); 21 CFR Part 312]. The CellTex AdMSC product is not the subject of an approved biologics license application (BLA) nor is there an IND in effect. Based on this information, your product violates the FDC Act and the PHS Act. “

      At that time I don’t believe Celltex as introducing its stem cells into interstate commerce, although now it seems they shipping them out of Texas into Mexico.

      The other issue that is quite important is having a BLA, which to my knowledge the clinics do not have as a general rule either.

      Perhaps because nearly 100% of drug manufacturers will introduce their drugs into interstate commerce, the FDA kind of assumes that to be the status quo and for the stem cell clinics that do point-of-care stem cell processing and interventions new FDA guidances are needed?

      This is a really important point you raise. Could others weigh in on operationally what the requirement for an IND means and when it is relevant?


      • Thank you Paul for the added insight.

        As I look more deeply into the FDA action against CellTex, I see that the key allegation is that a “valid biologics license must be in effect” (21 U.S.C 355(a); 42 U.S.C 26(a)). Unfortunately (for FDA; if CellTex hasn’t participated in “interstate commerce” [includes shipments from or to Korea or Mexico]) the statute still begins with:

        “(a) Necessity of effective approval of application (21 U.S.C 355(a); 42 U.S.C 26(a))
        No person shall introduce or deliver for introduction into interstate commerce any new drug, unless an approval of an application filed pursuant to subsection (b) or (j) of this section is effective with respect to such drug.”

        Once again the FDA is citing regulations based upon interstate commerce.

        My guess is that FDA could take action against CellTex because of the interstate commerce clause: shipments to or from Mexico or Korea (as you suggested may have occurred in previous posts) are likely to have occurred (anyone can correct me if this is a misstatement).

        I believe the FDA has remained silent on the “dubious clinics” which you call out because they (FDA) are not certain that they have jurisdiction. Individual states regulate doctors, and as far as I can tell, no one regulates surgeons (unless they operate across state lines).

        I think the real issue is outdated regulation (states vs. Fed rights) which are not designed to deal with current realities of medical practice possibilities (anyone can google a procedure and do it in their private practice [SVF derivation]; escaping FDA regulations as they stands).

        It would be wonderful if FDA could weigh in, guidance on which regulations apply would be very helpful.

        As always Paul, you provide a forum for the difficult questions facing “stem cell” therapeutics. The (significant) nuanced differences between classes of “stem cells” are difficult to navigate. Thanks for being willing to try (we’re not even close to discussing iPSC’s [the title of this blog).


        • I am not an attorney, but I think that J is right, both on the interpretation of INDs and on how regulations may be outdated. I also think that interstate commerce is probably specifically addressed to delineate between federal and state authority because the FDA is a federal entity- kind of like how jurisdiction goes to the FBI when criminals cross state lines.


          • It appears then that are some issues with the legal and regulatory language related to INDs.

            The thing I find ironic is that in my mind it would be entirely appropriate for the FDA in theory at least to use the IND mechanism to regulate investigational new drugs regardless of their planned (or not) introduction in interstate commerce. The BLA mechanism alone does not seem sufficient.

            Further, if one accepts the argument for the moment at least that the IND mechanism would be limited only to those cases that involve interstate commerce, then how would new experimental drugs be regulated that are not intended to be introduced into interstate commerce?

            Only by BLA?

            Certainly state medical boards have no role in drug regulation at the state level, only oversight of the physicians in their states.


            • BLA also appears drawn to interstate commerce:

              “The Biologics License Application (BLA) is a request for permission to introduce, or deliver for introduction, a biologic product into interstate commerce (21 CFR 601.2)”

              http://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/BiologicsLicenseApplicationsBLAProcess/

              This really seems to be a distinction between state and federal authority.

              Maybe state-level assurances are provided through state-level agencies? For example, the Food and Drug Branch of the California Department of Public Health?

              http://www.cdph.ca.gov/certlic/manfprocdistrib/Pages/DrugSafetyProgramPage.aspx


              • I think I may have an explanation on the interstate commerce puzzle and plan to do a post on this.

                It traces back to the FDA definition of “interstate commerce”. It is not quite intuitive according to the FDA:
                http://www.fda.gov/Cosmetics/GuidanceRegulation/LawsRegulations/ucm074248.htm#Interstate_Commerce

                Key verbiage: “Interstate commerce” applies to all steps in a product’s manufacture, packaging, and distribution. It is very rare that a cosmetic product on the market is not in “interstate commerce” under the law. For example, at least some of your ingredients or packaging most likely originate from out of state, or even out of the country. ”

                In other words, interstate commerce does not solely mean that the product that you produce then leaves your state. Rather it also seems to the FDA to mean that any element of the product originated from out of your state.

                So for example for production of SVF, the collagenase (traces of which remain in the final product) likely came from out of state. Does that mean the product involves interstate commerce? I guess so. The PBS you used came from out of state? The device you used? Etc.

                Thoughts?


              • Maybe request a Q & A with FDA Office of Cellular, Tissue and Gene Therapies (CBER-OCTGT) Director Celia M. Witten M.D., Ph.D.

                P:301-827-5102 F:301-827-9796


              • Paul, You may have found the answer, though the most recent case cited is from 1974.

                CPG Sec. 100.200 FDA Jurisdiction Over Products Composed of Interstate Ingredients

                http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm073820.htm

                “Over the years, the courts have reviewed the question of jurisdiction over products made from interstate components. The defense in these cases has been that the finished product is a new entity and FDA lacks jurisdiction until the “new” product is itself shipped in interstate commerce.

                The following court cases involving this question establish that FDA clearly has jurisdiction over finished products made from interstate components…”


                • Hi J,
                  Thanks for digging this up. Very relevant and seems to support the notion that the FDA has a lot broader power than some of the guidances might imply related to “interstate commerce”. I found my initial digging on this quite unexpected, but this info you found would seem to support the idea that a product has been introduced into interstate commerce if any element of its production involved other states. The finished product itself does not have to leave the state.


              • So the intent of your original post applies: why hasn’t the FDA stepped up to regulate these “dubious clinics”? These clinics, according to FDA, are “manufacturing” a “drug” (most likely with components acquired through interstate commerce) and administering to patients without IND or BLA, which the FDA thinks they have regulatory authority over. Something is still amiss (or at best opaque) here.

                Again Paul, thanks for hosting a forum for addressing these important questions.


                • Yes, something still doesn’t add up. I have heard various theories. Anyone want to throw some ideas out there as to why the FDA seems to be at best moving at a glacial pace on the mushrooming stem cell clinic industry?


    • Interesting that they said that immunosuppression was not required, especially considering that the cells were allogeneic. I have never heard of NSC transplantation without immunosuppression. How/why would they expect the MSCs and NSCs to evade the host immune system?


      • There’s a claim that embryonic or fetal stem cells and even in some cases more differentiated cells made from them are to some extent immunoprivileged and do not provoke immune reactions. I’m somewhat skeptical though and a number of such stem cells are used in conjunction with immunosuppression (e.g. StemCells, Inc. http://www.ipscell.com/2014/11/summaries-of-wafsf-super-stem-cell-vision-talks-hinton-tsukamoto-klassen-takahashi/). The CNS may also be less inclined to mount an immune response against an allograft, but systemic administration of allogeneic MSCs absent immunosuppression seems highly likely to invoke an immune response and most of such cells are likely filtered out in the lungs too. Harder to say about MSCs administered locally within a tissue.


        • I agree. Every single legitimate trial with allogeneic cells that I am aware of used/uses an immunosuppression regimen, and every time we did allogeneic transplantation of MSCs or NSCs in the lab, we used FK506 (tacrolimus) for immunosuppression (and still observed that most of the cells did not engraft and died fairly quickly). I wonder if they have any actual data to support their claim that immunosuppression is not required, or if it is something that they are just making up because they know that they don’t have to prove anything they say anyway?


          • So I think, everybody should store his own cells – from the teeth, from the placenta… there are several opportunities…


            • You can’t harvest that many cells out of teeth. It would take a lot of ex vivo expansion to get sufficient numbers of cells to do anything useful. As for the placenta and umbilical cord, except for in pediatric or congenital disorders, I am not sure what the advantages would be to storing the tissue/cells for 30+ years rather than simply taking bone marrow or lipoaspirate from the adult patient.


              • Thank you for your answer:

                I read the following article:
                http://onlinelibrary.wiley.com/doi/10.1002/stem.1909/pdf

                I have read:
                The mesenchymal stem cells from milk teeth should have a better quality than the stem cells from the fat and it should be possible to multiply them.
                So I think about storing the stem cells from the milk teeth of my children?

                If it is possible to expand the cells, this could be the best present for children?
                If it really will work some day …


              • Richie:

                I have worked with bone marrow and adipose MSCs and collaborated with those who work with dental pulp and gingival MSCs. I am not sure if it can be conclusively said that dental MSCs have better qualities than bone marrow or adipose MSCs, especially to the point where you would want to spend money freezing and storing the dental MSCs rather than harvesting fresh bone marrow and adipose MSCs if and when they are needed later on. Furthermore, the amount of expansion required to obtain a useful amount of cells may decrease their potency. With MSCs, every time they divide while being expanded, their “stemness” and potency is thought to decrease, which can be problematic if the starting number of cells is low and a large amount of expansion is needed. At this point, I personally don’t see any purpose or advantage of paying to store cells extracted from the deciduous teeth. This is the same reason why the American Academy of Pediatrics does not recommend storing stem cells from cord blood, placenta, umbilical cord, etc, unless the baby is born with a congenital defect that will require reconstructive surgery right away. If it were me, I would not spend the money on freezing the cells; instead, I would invest the money in my children’s education. I think that would be the best present for them.


          • Thank you for your answer and interesting insights concerning the stem cells in milk teeth. It is a great help.


  11. The main problem with Knoepfler seems to be that “unapproved” clinins are “potentially generating millions of dollars in income, all without FDA approval”.
    Patients should have a right to undergo the procedure given they understand the risk, especially in the case of autologous transplants.


    • The point is that patients are not accurately given an understanding of the risks, and reality of no actual benefit.

      The clinics administering these “therapeutic” treatments have not evaluated the risk or potential benefits of the experimental therapeutic, yet the patient is being asked to pay for such experimental treatment.

      Patients should not scammed out of their money.

      Buyer be informed as to what you are getting (or not).


  12. Paul:
    The issue of regulation of adipose tissue and its derivatives is a complex one that has moved beyond the old paradigm of “practice of Medicine” vs FDA regulation. The top most level of this argument is ultimately “what is safe therapy” for patients. To that purpose the FDA divided HCT/P into risk tiers (351, 361) each of which carry vastly different manufacturing requirements to ensure safety.
    Adipose and its derivative SVF are the classic “in between products” that fit neither category. Nobody will seriously believe that an autologous fat graft belongs in the same risk tier as a cultured allogeneic, genetically manipulated IPSC, yet under the new guidances it does in certain instances, though not others.
    The FDA is wrestling with this issue. Unfortunately in its last set of guidances it has adopted a definition of what is the nature of Adipose tissue and what is its natural and relevant function that is not reflective of biologic fact.
    The FDA asserts that adipose Tissue is EXCLUSIVELY “structural tissue”, and that its only natural and relevant functions are those of tissue padding and support. This denies 30 years of science documenting the endocrine, immune, and metabolic functions of adipose tissue, compared to which the structural function is relatively minor and secondary. The consequence of following the internal logic of this fallacy leads to puzzling classifications of lipoaspirated tissue being reinjected into a breast for reconstructive purposes constitutes “non homologous use” because the primary function of the breast is lactation (ignoring its physiological and psychological role as a secondary sex organ). Thus the same lipoaspirate injected into the face is not a drug, but in the breast it is. By the same token a very poorly processed lipoaspirate graft to the face can cause very real damage to the patient, but the FDA does not seem to think this is a problem.
    The FDA’s guidances may have been carefully thought out from a regulatory point of view, but not a biologic one.
    Responsible clinicians view both the excesses of the ersatz stem cell clinics and the non biologically based regulations of the FDA as impediments to patient care and safety.
    Adipose tissue autologous therapies are by themselves more active than inert “structural tissues”, and their tissue effects are sometimes only distinguishable (i.e. irradiated tissue, scleroderma) from SVF by degree, not quality. And nobody can seriously assert the risk profile of an autologous heterogeneous un-cultured population of a tiny proportion of mesenchymal stem cells (5-10%), precursor cells, and immune active cells belongs in the same risk pool as allogeneic homogeneous cultured that have undergone multiple culture passages and other genetic and/or epigenetic alterations.
    There is a way to get at a rational and scientific pathway approach to adipose tissue and SVF therapies. That is why I have always been a proponent of working together with the AABB to follow the same pathways other cellular therapies have.


    • Dr. Rodriguez, I agree with many of your points but would like to make one minor correction: most proposed iPSC treatments (such as the clinical trial currently in progress in Japan) are autologous, not allogenic.


    • Hi Ricardo. Thanks for the comment. It’s pretty clear that adipose is also a metabolic tissue, not just a structural tissue. But I’m not aware of any evidence that the stem and precursor cell component of adipose (i.e. what goes into the SVF drug product) originally in the intact fat tissue had systemic functions specifically derived from the stem/precursor component of the fat. It seems to me that those cells primarily are there to regulate tissue homeostasis of the adipose tissue.
      I agree that once cells are proliferated in a lab then that is a higher risk category than say fresh SVF immediately transplanted. Does that make SVF not a biological drug? Not necessarily. It just may be one with lower risk. Pluripotent stem cell-derived biologics are also drugs and have higher risks than probably even proliferated adipose or marrow stem cells (again depending on the labs and methods of course). Hopefully the FDA will understand variable risk amongst biological drugs and evaluate them accordingly.
      Perhaps we can all agree we need additional FDA guidance and clarity on these issues and that hopefully the FDA will be responsive to constructive feedback.


  13. We applied for and received an INAD to conduct a pilot study testing intra-articular SVF in dogs with OA. Our study is randomized, double blind, placebo controlled trial with quantitative outcomes assessment. We filled the study in 11 months (fully enrolled). Once the last two cohorts complete the six months follow-up exams, we will generate an estimate of the effect size so that we can plan a rigorous fully powered study to determine efficacy. We encourage the human stem cell clinics offering SVF for OA or joint disorders to apply to the FDA for IND and conduct clinical pilot testing: It is not onerous and addresses their critics concerns.


    • Thanks for the comment, Mark. Can you tell us more about your IND and study? Do you have links you could provide?
      Sounds of great interest.
      Paul


      • INAD: Investigation of new animal drug. no 12457. Pilot study to estimate effect size and safety of autologous SVF given into dogs with hip OA. Outcome using pressure sensitive walkway (quantitative primary outcomes); secondary outcomes are standard clinical instruments including range of motion, pain, joint space narrowing (JSN). In humans, JSN is the gold standard for monitoring OA progression. However, 2 yr follow up generally is needed to track JSN changes in humans. We don’t have tools with same resolution or long term data to know whether JSN will change in six months in dogs. NIH has an interest in large animal models of human disease. We applied to that PA because spontaneous OA in dogs is a good model for OA in humans (in my opinion), with the advantage that one year follow up of JSN in dog might compare to two year follow up in humans. Since SVF is provided to humans in fee for service model, as you indicated above, there is no reason not to track OA patients (before and after treatment). I am not discounting the testimony (e.g., found above) that SVF has an effect. Rather, Im suggest that we measure the clinical effect so that we can track progress of cell therapy field in terms of quantitatively measured effects . This provides standards to compare SVF’s effects to second gen cell therapy products in pipeline.


        • I think that this approach is really cool because it addresses a clinical need in companion animals while simultaneously providing large animal data that could provide hints and guidance for the management of human disease.

          I am wondering what the laws are like for veterinary clinical trials. For example, when does the INAD become necessary? Is it when you are recruiting privately owned animals for a study vs. purchasing them from a vendor? Also, is the procedure for securing the INAD similar to that of procuring the IND? Are the criteria equally stringent?

          Once you publish your data, could you please post them here as well? I am sure that many people would be interested in following this carefully controlled trial.


  14. I think it might be wise to take a deep breath and consider the case of Laetrile. Rather than explain in detail, I offer a link from Quackwatch http://www.quackwatch.org/01QuackeryRelatedTopics/Cancer/laetrile.html

    The belief among people in the US that Laetrile was an effective cancer drug was so widespread that the National Cancer Institute was pressured to do its own study. This substance, which contained cyanide, was useless for cancer, but did kill a few people prematurely and made some Mexican doctors very very rich.

    It’s difficult to keep a clear head about something that has such popular support. But popular support has nothing to do with whether a treatment actually works- it’s the desperation that leads people to believe that something will fix them.

    They think – after all, how could all those people be wrong?

    The answer: easily.


  15. Hi I have only just found your page and I am very interested to get in contact with Edward Ortiz who posted on January 27, 2015 at 7:29 pm. He said:

    “I live in Palm Springs, Ca., and had stem cell procedure done in June of 2013 in Rancho Mirage, Ca. for a lifetime problem of a serious asthma problem and was cured by Dr. Elliot Lander and Dr. Mark Berman. I can now breathe deep breaths and not shallow breathing and will not be concerned with heart ailments as asthma ultimately leads to heart failure due to lack of oxygen. I have seen what great things can happen.

    A friend of mine had a stem cell procedure done on his heart by another doctor in 2005 in Bangkok, Thailand.”

    Over the last 4 years I have had 2 stem cell treatments for a serious heart attack with 2 cardiac arrests I had back on 31 Dec2009. I am looking to go to Bangkok for more treatment and would really like to speak to the man who had his done there in 2005. If anyone can give me Mr Ortiz contact details I would much appreciate. Each treatment I have had by IV has improved both my heart and kidney functions by about 10% that do slowly retreat over time. My 2 separate treatments were done in New Zealand about 18 months apart. I an a firm believer that in time they will be able to repair my badly scared heart and kidneys. Most days I feel well, normal and can work. I’m happy to talk to anyone about my experience.

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