FDA warning points to tougher regulation of fat stem cells & clinics

FDA logoLast week I blogged about how the FDA had issued a warning letter to a series of three co-owned fat stem cell clinics across the US.

What does this FDA action mean on the broader stem cell clinic arena, particularly to those selling fat stem cells?

The FDA is still in the process of getting public comment and finalizing draft guidelines related to stem cell clinical products including fat stem cells aka adipose stem cells and stromal vascular fraction or SVF.

Even so, the FDA just issued this new warning letter at least partially related to SVF to a series of co-owned clinics in CA, FL and NY here in the US going under the names Irvine Stem Cell Treatment Center, Miami Stem Cell Treatment Center, and Manhattan Regenerative Medicine Medical Group.

In the letter the FDA explicitly calls SVF a biological drug in this context and mentions that there’s no IND and no BLA (for more on these key acronyms see here) at the clinics.

As discussed in the comments on my first post on this warning letter, the FDA language is a bit puzzling in the language used in the part calling the SVF a drug. The letter first mentions several target conditions as an implied possible reason for the definition as a drug and then only later indirectly mentions more than minimal manipulation as possibly involved. Non-homologous use is also mentioned. Overall this letter is not very clear. A helpful FDA reform would be a commitment to clear writing in its public communication.

Still the relatively unambiguous wording in the letter calling SVF a drug here is striking given that the FDA again has not to my knowledge finalized its guidance on SVF. It’s hard not to read the letter as meaning the FDA has every intention of defining SVF as a drug in many if not all cases.

This is a big deal because scores of stem cell clinics in the US are injecting SVF into patients on a daily basis without any FDA approval, licensing, etc. It’s not clear why these three co-owned clinics got the first FDA warning letter in the last few years on stem cells when there are all these other clinics doing very much the same thing. That’s also puzzling and leaves an important open question. More broadly as far as I know there’s no public information on how the FDA assesses which entities to focus its limited resources upon at any one given time.

What does this mean for all those other fat stem cell clinics out there? It’s bad news for them as the FDA could and really should be taking a close look at them too. The FDA is slow at times to take action as I’ve been critical of them about in the past, but once they get going, those not following the rules have reason to be concerned.

What about those recent still only draft FDA guidances (e.g. see a nice piece by Alexey on the situation with fat stem cells here)? I suppose they could change or take a long time to be finalized, but this warning letter can be viewed as a strong signal that the guidances are unlikely to change in their core points.

One of the largest collective users of SVF in the stem cell clinic world is Cell Surgical Network (CSN), with whom Irvine was previously affiliated. I contacted CSN more than a week ago by email for comment on the warning letter and to get their perspective on this development, but have not received a reply. To my knowledge, CSN has not been subject directly to FDA action, but I do not know when the apparent split with the Irvine clinics occurred.

Until more information about what the FDA is doing & thinking (at least as expressed by their written words) hits the  public domain, the key puzzles mentioned above will remain open for speculation. However, this letter possibly signals a major turning point for regulation of clinical use of adipose stem cells, particularly in the clinic realm.

Some patients unhappy with stem cell clinics

stem cell shot clinic

Screen shot from CBS Chicago TV segment of syringe filled with “stem cells”

Over the years I’ve heard from quite a few patients of stem cell clinics who feel very strongly about their experiences. Some have quite positive views on getting stem cell interventions, while others feel very negatively about the stem cell clinics. I’ve heard more of the latter kind of experience.

People often tell me that the stem cells from clinics only worked briefly at best and were too expensive. Another complaint is that the clinic responds to patient disappointment often by suggesting additional, expensive shots of stem cells for the “full benefit”. There is also sometimes a sense that the clinic claims while recruiting patients or on the Internet didn’t match the patient’s own experience.

A new report by Pam Zekman at CBS Chicago reflects the polarized views out there. Some they talked to were positive, but others were unhappy.

For example take the case of Charisma Cardine, who has been blind for 13 years, which the report describes as, “the result of a rare central nervous system disease.” 

“They told us that it was a 90 to 95 percent success rate,” Cardine says. “They said they worked with one other patient besides her before and they gained their sight back within two weeks,” her sister, Christiana James, adds. But Cardine’s $9,000 treatment at the Miami Stem Cell Treatment Center did not restore her sight.”

A stem cell doctor from a different clinic quoted in the article, Dr. Daniel Ritacca of the Chicago Stem Cell Treatment Center, has a positive outlook on their clinic’s treatment of more than 4,000 patients. One of his patients, Bob Leonard who suffers from MS, believes his stem cell treatment helped him. The Chicago clinic is part of the stem cell clinic chain, Cell Surgical Network.

For another stem cell clinic patient, Robert Heller who suffers from lung disease, his experience at yet another stem cell clinic, The Lung Institute (also see A Look Inside a Stem Cell Clinic Informercial by Professor David Brafman), was reported as not so positive in the article:

Heller paid $6,500 for treatments but says his condition only got worse. “”They give you a lot of BS and wishful thinking and selling you on hopes. False hopes,” he says.”

Those are strong words.

The reporter Zekman participated in a Lung Institute webinar, where reportedly claims were made that “71 percent of their patients” had seen increases in lung function.

Many in the research community are trying to get a better sense of the range of patient experiences at stem cell clinics.

Have you had a stem cell treatment at a clinic?

What has your experience been like?

Please share it in the comments. Or you can also email me directly (knoepfler@ucdavis.edu).

My new ‘neighbor’ in Sacramento: a fat stem cell clinic

Thomas A. GionisFor years I’ve been writing about stem cell clinics that sell non-FDA approved stem cell “treatments” to vulnerable patients right here in America.

These clinics have been sprouting up like mushrooms across the US and their numbers may be above 200 today overall. As a result perhaps it was inevitable that one would arrive in a locale near me.

Tomorrow, July 11, reportedly the Irvine Stem Cell Treatment Center will open a Sacramento, CA branch. The doctor there will apparently be Thomas A. Gionis (picture from press release). This private, for-profit clinic has no affiliation with UC Davis School of Medicine in Sacramento where I’m located.

The stem cell clinic Sacramento branch will sell transplants of fat stem cells in the form of something called stromal vascular fraction or SVF, which I believe is almost certainly a drug. To my knowledge this clinic and the large chain that it belongs to called Cell Surgical Network (CSN), do not have FDA approval to use SVF.

Both publicly and to me on this blog, CSN continues to argue that it doesn’t need FDA approval (herehere and here), but recent FDA draft guidances sure suggest otherwise in my view. Of course if the FDA never takes action on the use of SVF then how are we all supposed to interpret that? Without FDA action or finalized guidelines, is it formally possible that the FDA could back down on SVF?

This clinic will reportedly sell SVF to treat a dizzying array of conditions having nothing to do with fat:

“Emphysema, COPD, Asthma, Heart Failure, Heart Attack, Parkinson’s Disease, Stroke, Traumatic Brain Injury, Lou Gehrig’s Disease, Multiple Sclerosis, Lupus, Rheumatoid Arthritis, Crohn’s Disease, Muscular Dystrophy, Inflammatory Myopathies, and Degenerative Orthopedic Joint Conditions (Knee, Shoulder, Hip, Spine).”

To me as a scientist the use of SVF to treat all these very different conditions does not make good common sense.

It would also seem arguably to be quite likely be considered “non-homologous use” by the FDA, a standing that would also automatically make this a drug requiring FDA pre-approval. Non-homologous use means using a biological product of a certain kind that is not homologous (not the same or similar in origin) to the tissue being treated. For example, fat is not the same as the brain or other central nervous system tissue that is involved in several of the conditions on the clinic menu. Same goes for cardiac muscle, airways, etc.

The use of a non-FDA approved product in a largely non-homologous manner increases risks for patients. Note that these stem cell transplants are also very expensive with little evidence in the way of published data of benefit.

The CSN stem cell clinic in Sacramento will be located at the New Body MD Surgical Center, just about 10 minutes from my office. I plan on paying them a visit at some point. Let’s see how that goes. Will they let me in?

At mid-year, how are my top 20 stem cell predictions for 2015 doing?

Stem Cell PredictionsEach year towards the end of December I make predictions for the coming year as I did for 2015. In the past I usually make a top 10 prediction list, but for this year I made 20 predictions. Admittedly some of them may have been more hopes than predictions.

At mid-year today on June 30th, how am I doing? See below. Note that of course for some the jury is still out.

BTW, stay tuned for more on an upcoming update on the Japan IPSC macular degeneration trial where there seems to have been a (hopefully minor) hitch.

  • FDA ‘breakthrough’ on stem cells. FDA grants an investigational stem cell biological drug therapy the breakthrough status designation. Status: so far no luck, but still hoping.
  • Adult & pluripotent stem cell advances both impress. More encouraging publications and news on the clinical and translational fronts for both pluripotent and adult stem cell drug development including MSCs. Status: Definitely correct.
  • Doc training in stem cells. More new academic-related training programs for doctors to be true stem cell and regenerative medicine specialists. Status: so far no luck, but still hoping.
  • Big pharma’s big interest in stem cells grows further. Big pharma’s interest in stem cells & regenerative medicine continues to grow including at least one major development that might be takeover of a stem cell biotech or something else. That are some small stem cell biotechs that seem ripe as takeover targets. Status: Mixed bag. Both some positive and some negative signs on this.
  • RTT spread. At least one more state (and probably more) pass Right To Try (RTT) laws setting up a collision course between state and federal laws on investigational drugs including stem cell products. Status: Definitely correct. Tons of states moving on RTT.
  • Pro sports gets a bit more serious about dubious stem cell “treatments”. A pro sport players association or league acknowledges growing and difficult stem cell issues for players. Status: Mixed bag. 
  • More high-profile stem cell paper problems. At least one and probably more major stem cell paper problems pop up and could include retractions. Status: Yes, unfortunately (just see Retraction Watch on stem cells)
  • The UK Parliament OKs 3-parent baby tech. The parliament approves 3-parent/mitochondrial transfer technology, but more steps are required before it is practiced in humans. Status: Correct
  • Stem cell clinic chains Cell Surgical Network and Stem.md continue to grow for at least the first half of 2015 and probably beyond. They operationally challenge recent FDA draft guidances on adipose and minimal manipulation. Status: Correct
  • STAP-related news on the American front. We learn something on the US side of the story of the retracted STAP cell Nature papers. Status: Not yet, but stay tuned.
  • Muddier stem cell waters. More mixing of “legit” stem cell companies and researchers with the non-compliant side of the tracks. Status: Unfortunately correct
  • More stem cell paper debates and developments on PubPeer. A volatile situation continues with notable twists and turns. Status: Yep.
  • IPSC RPE safety. The IPSC-based RPE trial for wet AMD in Japan continues in 2015 without a reported safety hitch. Status: Probably Wrong (again stay tuned, but don’t freak out).
  • A stem cell biotech finds itself in a hairy situation. What a tangle. Status: stay tuned.
  • At least one patient is harmed or files suit for a dubious stem cell clinic treatment. This is a sad prediction, but unfortunately I think it is likely. Status: publicly not yet.
  • VSEL hell. There will be even more bad news for these Sasquatch of stem cells after the Weissman lab paper that seemed to refute these “very small embryonic-like” stem cells in 2013. What does this mean for NeoStem ($NBS) now known as Caladrius? Status: Nothing public yet, but I still expect it to be a bad year for VSELs. For Caladrius, I’m thinking the impact is minimal since their focus seems elsewhere under new leadership.
  • Celltex is going for an IND. This is an interesting development. Status: not publicly.
  • GOP on stem cells. Republications make some noise on stem cells or personhood. Status: not yet, but they are on CRISPR as my old soccer coach would say when I was a kid “like a duck on a june bug”.
  • FDA back in the game of taking action on dubious stem cell clinics. After a long quiet period in 2014, the FDA takes some action on dubious stem cell clinics. Status: depressingly, not yet.
  • Stem cell-based organs. The red-hot trend of bioengineering organs and tissues in part using stem cells as a material continues to develop. Status: Yes, organs and organoids are one of the hottest trends of 2015.

Popular Science stem cell clinic article itself raising some red flags

Popular Science stem cellsPopular Science recently did a piece on stem cell clinics that has raised some red flags. The concerns in this case are not necessarily about the clinics per se, but rather the actual article itself.

There are a lot of stem cell clinics out there and for years they had a pretty consistent strategy of avoiding media attention. It’s almost as if they had a secret “fly under the radar” club to avoid negative PR.

However, today’s stem cell clinics are bolder and have adopted a new strategy: actively use the media as a tool for positive PR.

For instance, there is the Gordie Howe-Stemedica case that seems to keep on giving and giving PR to Stemedica and its Mexican partner Novastem. Amongst other things, they do some non-FDA approved stem cell interventions in Mexico. After months of positive PR on the Howe story for Stemedica including from Howe’s family who talked up the clinic, we all learned that the Howe family had become investors in Stemedica at some point.

Popular Science has, in my way of thinking, fallen into this kind of stem cell clinic PR web with a recent piece. Writer Tyler Graham worked for a long time on this story on stem cell clinic chain, Cell Surgical Network (CSN). During that time he contacted Leigh Turner and me for assistance on the story and quotes.

Tyler also became, by his own disclosure in his piece in Popular Science, a patient of CSN, but we were not made aware of that. Tyler reports in his article having got a therapy from CSN doctor Mark Berman for a long-term, very troublesome back condition and gives a remarkable account of how the treatment apparently helped him. A cure is suggested.

Then there is the title of the piece: THE CURE-ALL.

There is no question mark on that title and the implication in the article is that the writer was cured of his back problem by CSN. The net result of this article is likely a drive of new business to CSN.

To his credit, Tyler does raise numerous questions about stem cell clinic offerings. He also reports on another patient (Lamon Brewster) who in the long run was not helped by CSN so that part of the article is good for balance, but overall my sense is that the article is very problematic.

The piece has some statements that sound promotional:

“That’s not to say Berman is doing anything illegal by offering a treatment he doesn’t fully comprehend. He’s not. He’s not even doing anything unethical. He is healing patients who could not be healed.”

These statements are questionable.

In the end this article is a big disappointment.

Because some high profile people have received free treatment (e.g. Gordie Howe) from stem cell clinics I asked Tyler if he received any kind of discount, free treatment, or other benefit from Dr. Berman or CSN, but got no reply. I also asked the fact checker for this story, Rebecca Geiger, about this question, but she did not reply either.

If I do hear from them I will definitely post it. It could well be that full price was paid and there were no other perks, but it was a reasonable question to ask.

If you want to see a recent in my view more balanced, investigative piece of journalism on stem cell clinics, I’d recommend taking a look at the great piece by the Associated Press (AP) by Matt Perrone.