More than minimally manipulated

More than minimally manipulated is an FDA term that means that cells are processed beyond a certain point. 

While the Celltex controversy was unfolding down in Texas, the International Cellular Medicine Society (ICMS), a group dedicated to applying stringent guidelines, announced the appointment of plastic surgeon Ricardo Rodriguez as its new president. will be the third leader of this organization, which has shown a frankly astonishing ability to project its patient centric messages (and those of its previous leaders, sports medicine doctor Christopher J. Centeno, and chiropractor/epidemiologist Michael D. Freeman) in major media and across the internet. 


But what exactly is the ICMS about, how did it burst so suddenly onto the stem cell scene, who are its leaders, and what motivates them? The tale is long, so I'm afraid I'm going to need to ask a bit more of your time than usual to explain.

ICMS gets it's mail at a PO Box, like many small organizations. Also like many small non-profits without funding, it's true presence is on the internet. 

The Salem P.O. box is a convenient place for ICMS executive director, Salem-based David Audley, to pick up the mail, and just one hour by car from Oregon Health Sciences University in Portland, where former ICMS president, Michael D. Freeman (2009-2012), teaches forensic epidemiology. Freeman, originally a chiropractor, More recently, he seems to be putting this knowledge to frequent use as an expert witness in various cases, including testifying for the defense in the Casey Anthony trial, and giving lectures on "Exposing, defusing and debunking junk science" in Los Angeles this January.

I don't know what led Freeman out of chiropractic and into the arms of epidemiology, expert testimony, and his longtime partnership with Chris Centeno, owner of Regenerative Sciences (of Regenexx™ and USA v Regenerative Sciences fame), but PubMed shows their first co-authored publication to be from 2004 ("Waddell's signs revisited?"). This co-authored comment in Spine  and their next six papers have nothing to do with stem cells, but rather various forms of spinal injury, with a focus on spine trauma. For the past few years I thought this was anomalous, and not particularly worth commenting on.

But then last month I stumbled across some real expert testimony, by Dr. Muschler and Freeman, in the FDA vs Regenerative Sciences case. But for anyone interested in seeing what a barn burner of back and forth between these two experts only need to look as far as Centeno's response to this article:

Dr. Muschler established his own standard for what constitutes effective research. Unlike our procedure, where we went through two years of an IRB where we didn’t charge patients, Dr. Muchler’s competitive procedure that spawned his “Cellect Device” was used by surgeons solely based on a study in dogs (i.e. without any human use or IRB oversight). This is despite the fact that under current FDA rules, the device more than minimally manipulates a bone graft sample by allowing stem cells to attach to the sample, as its stated goal is to alter the biologic characteristics of that bone graft. After that, it was used in thousands of patients before a single human trial was performed. When that study was finally published, it wasn’t an RCT with a placebo; instead it was a comparison trial similar to the one we published on our procedure (see http://www.box.com/s/vzlh0sqt3v987m33vnfj).

Centeno and Freeman were also leaders of a separate, now-defunct organization (Spinal Injury Foundation) prior to becoming the first and second president of the ICMS, and said organization was tasked with, among other things, providing the institutional review of a body of research behind Centeno's Regenexx™ Freeman responded to the FDA's expert declarations here, and Regenerative Sciences posted a chronology here.

Freeman and Centeno: the early years

At this point in the story, I have to give credit to an anonymous friend of the blog who pointed out that the Spinal Injury Foundation itself evolved from a different website, Whiplash 101. Centeno also founded an (also now-defunct) online Journal of Whiplash and Related Disorders, for which he and Freeman, served as co-editors-in-chief.

http://web.archive.org/web/20050210122622/http://whiplash101.com/

Centeno and Freeman's Spinal Injury Foundation ran awareness days and other fundraisers including, in 2007, a chance to drive a Lamborghini, Ferrari, Bentley, or other speedmobile around a race track in the Rockies. The promotional page for the event included the cautionary text: "If you can't find a car you like, consider psychiatric help or high-dose antidepressants."

Snap your neck for whiplash!

It was in around 2005 that Centeno showed visible symptoms of the stem cell itch (his first stem cell paper was published the following year). We know this because 2005 was the year he sold the Colorado professional corporation known as "Christopher J. Centeno, M.D., P.C."  to Florida-based company PainCare Holdings for $3,250,000 in cash and 1,132,931 PainCare shares valued at $3,750,000. The PainCare deal turned rancid after that company was accused of overstating its revenues, and became subject to multiple class action suits. Centeno was able to regain his assets.

Not long after this settlement, Centeno and Freeman started the first version of the ICMS, known as the American Stem Cell Therapy Association (ASCTA) at www.stemcelldocs.org. This group, whose founding members included Freeman, Centeno, and Centeno's partner John Schultz, espoused the same basic set of values that characterizes the ICMS, including an emphasis on the use of autologous stem cells as teh practice of medicine.

Whatever the case, the ICMS' general strategy seems to me to have consisted from Day One of: 1) the promotion of the use of stem cells as the practice of medicine.

In a remarkably short time, the ICMS became a credible organization, complete with various guidelines, an Offshore Clinics Report another patient portal (Stem Cell Watch), a newsletter, a Treatment Registry, which is at 750 registered patients and counting, and a Clinic Accreditation Program for clinics. The organization also recently announced a deal with an insurance company to provide malpractice insurance for their members. This, in my view, may prove to be one of the most valuable member service ICMS has introduced to date.

The accreditation program allows clinics to certify taht they are following guidelines. The first outfit accredited by the ICMS is the Regenerative Medicine Institute of Tijuana, Mexico. The ICMS process, took less than a year (the RMI application for accreditation was announced on March 15, 2011, and the ICMS approval announced on February 24, 2012). In the more recent release, ICMS executive director David Audley praised the clinic, saying, "The safety profile has been excellent. We have tracked patients over at least two follow ups and a minimum of six months and not seen a single cell-related adverse event." 

ICMS has also investigated clinics when adverse events were reported. This occurred when the organization announced investigation of the death of a patient treated at the same clinic, and then CNN later announced that the clinic's stem cell treatment didn't cause the death of the  two patients. The group's website issued a release noting:

The investigation of the deaths was led by ICMS Board President Dr. Michael Freeman, forensic epidemiologist and Affiliate Professor of Epidemiology at Oregon Health & Science University School of Medicine and Adjunct Associate Professor of Forensic Medicine at Aarhus University. The investigation involved extensive interviews and review of documents, as well as consultation with experts in clinical applications of stem cells, including Dr. Keith March, Professor of Medicine and Director of the Vascular and Cardiac Center for Adult Stem Cell Therapy at the Indiana University School of Medicine. As a result of findings uncovered during the investigation into the patients’ deaths, the ICMS initiated an on-site evaluation of ethical and clinical practices of RNL Bio, conducted by Dr. Glenn McGee, John B. Francis Endowed Chair of Bioethics at the Center for Practical Bioethics.

The ICMS has made the following findings:

• The death of patient JJJ, which occurred nearly 2 months after his last stem cell infusion, was unlikely to have been caused by either the stem cells or the procedures used to administer the stem cells. The specific cause of Mr. Jun’s death is currently unknown as no documentation has been released with this information.
• The death of patient LSK, which occurred on the same day as the stem cell procedure, was likely to have been caused or triggered by the stem cell procedure. The cause of death was due to a pre-existing blood clot that traveled to the lungs, and may have been precipitated by the procedure used to infuse the stem cells, or less probably, from a clot formed by the cells.
• No evidence was found to suggest that inaccurate information caused either patient to give consent to medical procedures that they otherwise would not have given. A review of all relevant forms, chart notes, correspondence, and interviews suggests that both patients were provided sufficient information to give appropriate informed consent, and both did give consent.

The ICMS has accepted other applications as well. Take World Stem Cells, LLC, for instance. Located in Cancun, Mexico, this clinic flies the ICMS badge right on the top page of its website, and applied for accreditation last May. 

http://worldstemcells.com/stem-cell-therapy-conditions.html

Chris Centeno has been keeping busy after being replaced by Freeman as head of the ICMS and is now locked in a legal fight over an injunction the FDA sought against his company Regenexx. He has licensed to partners in Argentina and China, and set up a stem cell treatment subsidiary in the Cayman Islands. He is also a planning committee member and speaker for this year's one-day ICMS-sponsored session in Hollywood, FL, held in conjunction with the annual meeting of the Age Management Medicine Group, alongside other such luminaries as Jeffry S. Life. 

Yes, that Jeffry S. Life.

It is too soon to say what will happen under new leadership, and best of luck to Dr. Rodriguez and the latest generation of ICMS leaders in setting the group on a course to science-based medicine.