Just how safe are stem cell transplants?
Is an autologous stem cell transplant always safe?
Is it really true, as one stem cell transplant doc once said of autologous stem cell treatments, that “the worst thing that could happen is the treatment won’t work”?
Are adult stem cell treatments by definition safe?
The reality is that there are more questions than answers about the safety of stem cell treatments, and each treatment (depending on the institution, the doctor, and the patient) is likely to have a variable and perhaps unpredictable level of safety.
However, in this post I cite just three papers from 2012 that raise enough safety concerns in my mind to make me think patients should use extreme caution in decision-making.
In the first paper, Jonsson, et al, the researchers report termination (for safety reasons) of a study for the treatment of critical limb ischemia using autologous peripheral blood stem cell transplants. The study found evidence of some efficacy, but in about half of patients there were such severe complications that the study overall was terminated. Complications included heart attacks and thrombosis (blood clotting). Limitations of the study include its small size (N= 9 patients) and the age of the patients (mean ~77 years old). Still one clear take home message from this study is that “autologous” and “adult stem cells” do NOT automatically equal safe.
In the second paper, Alderazi, et al, the scientists report a case study (so by definition a limitation is that N=1 patient) in which a 17-year-old girl nearly died from intrathecal (in the spine) and IV transplants of stem cells for MS. She received both autologous and allogeneic treatment, with the procedures done in Costa Rica. The girl developed catastrophic demyelinating encephalomyelitis after the treatment, a condition where one’s immune system attacks the brain.
In the third paper, Martin-Padura, et al, researchers report that adipose stem/progenitor cells typically used in fat transfer and stem cell procedures, have a powerful pro-cancer function. What these means is that transplants of adipose MSCs could stimulate other cells to become cancer.
Bottom line. These papers each have limitations and by no means are they telling us that adult stem cell treatments are inherently dangerous in every case, but they should dispel the myth that the cells are inherently safe. These papers also illustrate why patient follow up, which for-profit clinics so often fail to do, is so critically important and should last years if not decades.
Paul, you wrote that you’d be reading and discussing the data:
“Thanks for the comment and the 10 papers, Glenn. I’ll go through them and let you know what I think.”
Is that going to happen?
Regards,
Glenn
Glenn & all,
The Knoepfler Lab Stem Cell Blog is an established source for researchers, investors, and layman to interpret the latest findings and thoughts from around the field. Not to speak for PK, but the piece appears to be designed to provoke further investigation–not as an invitation to patronize in the manner that GM has so awkwardly dragged us through when advertising personal credentials.
As an investor, I am looking beyond safety when comparing cell therapy approaches. For the time being, all these cell types have potential. However, these adult cells are now being used as controls when observing more potent cell types. iPS cells might be the future and could help get treatments through regulation, but hESC will be the gold standard(potency,upscaling, etc) until those issues in iPS are figured out. In the end, I think the two approaches will have to coincide for the various systems and cell types in the human body. Adult cells have been around for four decades with minimal impact.
Speaking of adult cells and the companies that sell them without FDA approval, well they should be shut-down and those responsible thrown out of the country. The entire industry has been held back by novice, greedy salesmen pitching to the most desperate of cliental and spreading cherry-picked studies to move their agenda. For shame.
It doesn’t matter. FDA efficacy/safety results will bring large investment, and that will decide who the winners are…good luck with that –wherever you hide your business.
This idea that “adult cells have been around for four decades with minimal impact” is not entirely true. Oncologists for instance have utilized bone marrow transplants in some of their patients often times successfully for many years. (Since the late 60’s) Anecdotally, adult stem cells have seemingly helped three people (one a smoker) that I know with regard to their arthritic symptoms and have saved two of them from much riskier knee and hip replacement surgeries. Of course these surgeries (despite their invasivene$$) are in the main stream of medicine but have also been known to cause blood clots and many other problems particularly in smokers past the age of 65.
I hope people understand the potential threat that successful utilization of adult stem cells poses to the very real financial interests of the current medical/research industrial complex. And this includes the FDA and the Pharmaceutical Industry. This is in part because adult stem cells are entities that generally cannot be patented. Patenting involves lots of money. And, big Pharma tend to invest only in that which is promising in terms of a return on research dollars spent by them. (Go ahead. Call me a conspiracy theorist. But you can read about this very real phenomenon in Deadly Monopolies by Harriet Washington for confirmation)
Given the amount of money big Pharma spends on bio-medical research, it is then little wonder why the success of adult stem cells are not further written or even heard about. Small stem cell clinics do write about the success of their autologous stem cell and platelet rich plasma therapies in some of the literature. And perhaps smaller clinical trials can be conducted in some stem cell clinics. (Like Regenexx) . Read Chris Centeno MD’s work by doing a PUBMED search on his name)
But since these clinical studies don’t usually involve enough or even any capital from big Pharma and/or many other investors, negative perceptions about stem cell clinics in the U.S. and abroad can develop as a result. Many of these clinics simply cannot afford in their practice of medicine the equipment and personnel needed to conduct very rigorous multi year double blind placebo controlled studies. So they don’t get the splash in the press that the big money can afford to pay for. To my knowledge, it is the research into stem cells of the decidedly embryonic type that have had “minimal impact” despite the comparatively larger quantities of money spent on this type of controversial science.
Personally I don’t feel as though my own body parts need to be subjected to these sorts of rigorous and expensive medical/scientific experiments which will just drive the cost of medicine up even further than it already is. I’ll put my faith in my own bone marrow and adipose tissues and the cells they contain that are not capable of bias. And, given the corporate control of medicine these days, it will be some time before I place the same amount of trust into any scientist or investor representing a corporately funded laboratory with an obvious financial ax to grind.
Article excerpt on McGee (link below):
In fact, some of the accomplishments McGee cites on his 48-page curriculum vitae, on Web sites he manages, and in news reports are not quite what they appear at first glance. A press release issued by Albany Medical College announcing his March 2005 arrival notes that he had also just been “named chief of the Office of Bioethics for the New York State Department of Health,” a claim that McGee repeated during an interview last week. “When I moved to Albany,” he told ScientificAmerican.com, “I was named chief of bioethics by the Wadsworth Center” at the New York State health department.
“Dr. McGee is experiencing delusions of grandeur,” says Jeffrey Hammond, a state health department spokesperson. “Let’s set the record straight: McGee was a volunteer, not an employee. He gave himself the lofty title of chief of bioethics and as a volunteer was not compensated for his time.”
Scientific American: An Unethical Ethicist? http://www.scientificamerican.com/article.cfm?id=glenn-mcgee
Wow. Somebody must really be worried about their misrepresentations of data to reprint an inaccurate 5 year old article. Be careful though. While the statute ran out on the article, it didn’t run out on your post. I was in fact Chief of the Office of Bioethics, a position I was invited to hold by Larry Sturman, head of Wadsworth Labs, the public health labs for all of NY. He offered to pay my entire salary if I’d come to work with him instead of at the medical school. On “basement one” floor there is an office clearly marked “Office of Bioethics” created for me to do my work, and my badge and title, which the PR guy knows I obviously couldn’t “give myself,” are not in dispute. If you’re going to reprint this without fact checking, Paul, it becomes your statement. But the more interesting thing is that you’re so desperate to turn a referendum on your inability to present honest data about MSCs into a series of ancient ad hominem attacks. I guess you didn’t like my interview terms.
XXXXX (note edit here)
Regarding Glenn McGee (Nature, Feb 2012) …
“Imagine if the Editor of the New England Journal of Medicine took a job as Vice President at Merck, and the Mass Medical Society asked him to stay on as Editor, opining that the conflicts of interest would be manageable. One might rightly wonder, ‘What are these people smoking?’,” says John Lantos, director of the Children’s Mercy Bioethics Center in Kansas City, Missouri, and a past president of the American Society for Bioethics and Humanities.
—
But during McGee’s tenure as editor-in-chief of the AJOB, four editors are known to have resigned from the editorial board because of differences in opinion over how the journal handles conflicts of interest.
—
McGee already had a connection with RNL Bio. In 2010, two patients died following injections of RNL’s cells. McGee, working for stem-cell lobby group the International Cellular Medicine Society, based in Salem, Oregon, helped to conduct an investigation into the company. This concluded that only one of the two cases was likely to be related to the injections, and because the patient understood the risk the company was not culpable.
Jin Han Hong, the then president of RNL’s US subsidiary, admitted in 2010 that there was no clinical-trial evidence proving that these treatments are effective.
http://www.nature.com/news/editor-s-move-sparks-backlash-1.10068
On January 5, 2012 John Lantos, having been informed of the plans implemented before I left my journal, wrote that the plan was just fine.” His later feigned outrage has been established to be simple lies. Lantos also demanded $25,000 per year to edit a spin-off AJOB Journal, which I would not pay. Lantos was also replaced in his job as John B Francis Chair by … me. Do the math.
ZERO editors resigned while I was EIC of AJOB. Four members of the editorial board resigned. Carl Elliott (bye!), Hilde Nelson (who was trashed in a peer-reviewed article calling her unethical), Lantos resigned (bye!) and somebody else I can’t remember. More interesting is that ZERO other editorial board members resigned in the wake of what Lantos calls a “New England Journal” level issue. None. Leigh Turner practically crusaded for it. Nobody. Gosh I wonder why.
RE: RNL. It has been well established by the one person who is ever quoted on the matter that I never investigated any issues of cause of death in any stem cell matter ever. My report on ethics is on the web. I was not paid for it and it certainly wouldn’t have won me a job. Hence Carl Elliott was the first person in the history of Slate magazine to have an article outright retracted for factual inaccuracy and unfairness, which only a moron would say was the result of “legal pressure.” I’m a BIG threat to the WASHINGTON POST. Not.
And again…when the facts you spew are wrong, resort to ad hominem. But this time guys, everyone’s already read the nasty stuff in the press. They have drawn their conclusions. Either they trust that I am a good person, or they’ll believe your completely incoherent data analysis on the grounds of ad hominem alone. I’m betting you’ve played this card too many times, “David C.” And if you are who I think you are, don’t forget: you get retracted too…
Glenn,
Can you tell us more about RNL Europe? I’d love to host a Q&A interview with you on it on this blog. I’d post your answers verbatim as long as they don’t violate my blog policies (which I think is unlikely to be a problem).
As CEO of RNL Europe it seems there would be no one who is more ideally positioned to tell us what it is all about than you and why not give the world more info on what your company is all about?
Or is your statement about “silence” killing science only applying to others? Let’s talk openly.
Paul: Great idea. I’d love to answer your extensive questions, right after 1) you answer my posts, and 2) I interview you without restriction, for your blog, without edits, and you 3) interview a well-cited scientist of my choosing, with >50 pubmed adult cell publications, providing them a full opportunity to review your many data claims like the lovely “3 reasons to be terrified” post. Then we can *absolutely* do that, provided I make an opening statement to clarify the obvious reason for the interview, and provided that you make commenters aware of German libel law (as you can see, you’ve already posted two libelous posts below). Sound good? If so, you’re welcome to continue to try to take the attention off of yourself and the voluminous data above – which thoroughly disproves every accusation you make – and turn to a transparent attempt to show me to be unqualified. Good luck.
The reference in the comments about Tysabri “being as safe as driving to a hospital in Houston” stuck out like a sore thumb! I have MS & when I questioned my neuro on the risk of taking Tysabri his exact words were, “You drove here didn’t you? You had as big of risk in that as any taking Tysabri!” Was this part of the sales training from the drug company or what? Too weird! Tysabri has proved to be a deadly drug and new side effects continue to surface like CNS Herpes/Varicella Infections. There is no doubt all the FDA drugs on the market for MS are high risk. It leaves MS patients with few and risky options.
Tracy…You have my deep sympathy. But you are fighting the wrong war against the wrong people. The authority in the matter is the FDA. Why bother to explain to @leighgturner what the drug is. If he cared, he’d have ever discussed anything other than evil evil stem cell people, whose “product” produces MS risks that include … wait … one highly suspicious case report of a iatrogenic event that occurs regularly in MS patients anyway. Pales in comparison to the known risks of the drugs you know. But he plainly could care less (if the definition of care=writes about risks comparatively and fairly and with any statistical analysis and after peer review). The present issue of Nature does seem to understand your situation. And the FDA is not without compassion. It remembers when dying HIV/AIDS patients stormed fences to get access to medications. Talk to THEM. To CBER. To Nature. There is a deliberate effort to confuse tens of thousands of patients and parents about “who to trust.” A national MS stem cell group praised 60 minutes for stem cell reporting because it unearthed a crazy man on an island. So naturally, the most common comment is “we’re confused,” not “help us learn the literature.” And the people you ask for help, well, lie.
Demand that stem cells be offered only after safety is demonstrated to be no more an issue than the risk you face every day, and demand that efficacy is evident to meet equipoise – no worse, based on present evidence, than the present standard of care in the mind of your competent physician.
But never forget that there would be no major cancer center in the United States were there not patients who elect to participate in trials when they have no other options. And don’t think those giant glass buildings for embryonic cells in California, ripped apart in an editorial by California’s leading stem cell scientist, represent cures. Don’t doubt the millions, no, billions spent on care given to cancer patients while enrolled in last ditch Phase I trials.
I don’t doubt that Leigh Turner would love to shut down every risky clinical trial. He and Carl Elliott seem, *by their own account*, however, to draw their salaries from the most unethical medical center in America. Keep that in mind when they call out people like me for having a COI.
Patients with no hope are offered platitudes by clowns who say they care so much, and talk about how much they respect your decision, but then call you victims. They repeat over and over a position from the FDA that the FDA doesn’t even hold. If substituting one woman’s cytoplasm for another is not minimal manipulation under FDA rubric, then it is awfully hard to see how “minimal manipulation” can be the metric for determining whether autologous stem cells are something that should trump the FDA’s long ignored responsibility to regulate every kind of reproductive engineering where there isn’t anything like outcomes data.
I call this STEM CELL EXCEPTIONALISM. It’s lethal. But it isn’t the FDA doing it. It’s scholars from areas other than MSCs who never state anything about their philosophical position on exceptionalism…they just say “unsafe unsafe.” Get George Daley to disclose his COI at Harvard, and no reporter worth a damn will ever quote him again on safety…yet he is the only serious scholar ever quoted on the issue, despite a total lack of publications on MSC safety. It’s not reasonable.
Crazy offshore clinics are bad. People do bad things. Personal disclosure: I’m sure that those who said that I was evil for editing my journal at the time, The American Journal of Bioethics, for 15 days during the transition to work at a stem cell company were TOTALLY speaking from sincere concern (even if they were, in order, a person described as unethical in the journal, a person who demanded to be paid to edit one of the journals and in whose job I replaced him, and Carl Elliott, who has clashed more with me than anyone ever clashed with anyone in bioethics). Assume good motivation. Assume COI. But first and foremost recognize that when someone starts tearing into the character of a person presenting facts, you’d probably do well to wonder whether ad hominem attacks are designed to procure press coverage or to help you.
I wish there were something I could suggest…but the group where I work is doing research and working toward the science that will deal with these issues. I neither hold equity nor an MD, and I’m no longer an ethicist…business is infinitely less immoral these days. But I would suggest again that you talk to the FDA. Talk to the advocacy groups. And wave that Nature editorial in front of the people who count. Silence kills science, imho.
I’m sorry but this is a load of BS. The first paper you cite has the following: “Four patients experienced some degree of improvement with pain relief and/or improved wound healing and ABI increase. One patient was lost to follow up due to chronic psychiatric illness; one was amputated after two weeks. Two patients had a myocardial infarction (MI), one died. One patient died from a massive mesenteric thrombosis after two weeks and one died from heart failure at week 11. Improved patients showed variable effects in cytokine-, growth factor- and local metabolic response.”
So you’re telling me the stem cell transplants were responsible for chronic psychiatric illness? Limb amputation in an older patient with pre-existing CLI? Mesenteric thrombosis (from a leg injection??)? Heart failures in an older patient after 11 weeks (again from leg injections???)? These are all old, sick patients so to imply that these adverse events were due to injections of cells into their leg muscles is quite a stretch.
As for the adipose paper, so what? That adipose cells can be recruited for neovascularization is well known and occurs from fat depots in situ. The idea that administering these cells will somehow cause more cancer is again, to put it mildly, quite a stretch.
Thanks for the comment, Steve. I suppose BS is in the eye of the beholder/reader of papers.
I thought perhaps that in your citations of the barometric studies to warn off people from seeking out stem cells, you might want to include just a tiny number of the studies in 2012 alone that would seem to require your attention. I think frankly you might also want to state that you are not an MSC researcher but work in the competitive technology of iPS, in a group that describes itself as “building bridges to cures” ostensibly through its own technology. See below with all due respect.
1.
Stem cell transplantation in amyotrophic lateral sclerosis patients: methodological approach, safety, and feasibility.
Martínez HR, Molina-Lopez JF, González-Garza MT, Moreno-Cuevas JE, Caro-Osorio E, Gil-Valadez A, Gutierrez-Jimenez E, Zazueta-Fierro OE, Meza JA, Couret-Alcaraz P, Hernandez-Torre M.
Cell Transplant. 2012;21(9):1899-907. doi: 10.3727/096368911X582769.
PMID: 23356668 [PubMed – in process]
Related citations
2.
Therapeutic Outcomes of Transplanting Autologous Granulocyte Colony-stimulating Factor-mobilised Peripheral Mononuclear Cells in Diabetic Patients with Critical Limb Ischaemia.
Mohammadzadeh L, Samedanifard SH, Keshavarzi A, Alimoghaddam K, Larijani B, Ghavamzadeh A, Ahmadi AS, Shojaeifard A, Ostadali MR, Sharifi AM, Amini MR, Mahmoudian A, Fakhraei H, Aalaa M, Mohajeri-Tehrani MR.
Exp Clin Endocrinol Diabetes. 2013 Jan;121(1):48-53. doi: 10.1055/s-0032-1311646. Epub 2013 Jan 17.
PMID: 23329572 [PubMed – in process]
Related citations
3.
Mesenchymal stem cell transplantation in multiple sclerosis.
Cohen JA.
J Neurol Sci. 2013 Jan 4. doi:pii: S0022-510X(12)00633-8. 10.1016/j.jns.2012.12.009. [Epub ahead of print]
PMID: 23294498 [PubMed – as supplied by publisher]
Related citations
4.
Accelerated and Safe Proliferation of Human Adipose-derived Stem Cells in Medium Supplemented with Human Serum.
Josh F, Kobe K, Tobita M, Tanaka R, Suzuki K, Ono K, Hyakusoku H, Mizuno H.
J Nippon Med Sch. 2012;79(6):444-52.
PMID: 23291843 [PubMed – in process] Free Article
Related citations
5.
Therapeutic potential of autologous stem cell transplantation for cerebral palsy.
Purandare C, Shitole DG, Belle V, Kedari A, Bora N, Joshi M.
Case Rep Transplant. 2012;2012:825289. doi: 10.1155/2012/825289. Epub 2012 Oct 4.
PMID: 23259143 [PubMed] Free PMC Article
Related citations
6.
A novel, minimally-invasive technique of cartilage repair in the human knee using arthroscopic microfracture and injections of mesenchymal stem cells and hyaluronic acid–a prospective comparative study on safety and short-term efficacy.
Lee KB, Wang VT, Chan YH, Hui JH.
Ann Acad Med Singapore. 2012 Nov;41(11):511-7.
PMID: 23235728 [PubMed – in process] Free Article
Related citations
7.
A phase II trial of autologous transplantation of bone marrow stem cells for critical limb ischemia: results of the Naples and Pietra Ligure Evaluation of Stem Cells study.
Schiavetta A, Maione C, Botti C, Marino G, Lillo S, Garrone A, Lanza L, Pagliari S, Silvestroni A, Signoriello G, Sica V, Cobellis G.
Stem Cells Transl Med. 2012 Jul;1(7):572-8. doi: 10.5966/sctm.2012-0021. Epub 2012 Jul 6.
PMID: 23197862 [PubMed – in process]
Related citations
8.
Stem cell therapy: A clinical trial of stroke.
Bhasin A, Padma Srivastava MV, Mohanty S, Bhatia R, Kumaran SS, Bose S.
Clin Neurol Neurosurg. 2012 Nov 23. doi:pii: S0303-8467(12)00533-1. 10.1016/j.clineuro.2012.10.015. [Epub ahead of print]
PMID: 23183251 [PubMed – as supplied by publisher]
Related citations
9.
Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.
Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, Brinker JA, Breton E, Davis-Sproul J, Schulman IH, Byrnes J, Mendizabal AM, Lowery MH, Rouy D, Altman P, Wong Po Foo C, Ruiz P, Amador A, Da Silva J, McNiece IK, Heldman AW.
JAMA. 2012 Dec 12;308(22):2369-79.
PMID: 23117550 [PubMed – indexed for MEDLINE]
Related citations
10.
Rationale and design of the first randomized, double-blind, placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal Stromal Cells in chronic ischemic Heart Failure (MSC-HF Trial). Mathiasen AB, Jørgensen E, Qayyum AA, Haack-Sørensen M, Ekblond A, Kastrup J.
Am Heart J. 2012 Sep;164(3):285-91. doi: 10.1016/j.ahj.2012.05.026.
PMID: 22980293 [PubMed – indexed for MEDLINE]
Related citations
Thanks for the comment and the 10 papers, Glenn. I’ll go through them and let you know what I think.
I do work on iPS cells as well as ES cells, neural stem cells, and cancer stem cells, but you are right that I do not work on MSCs. However, I do not see these as competing, but rather complementary technologies.
If we are exchanging advice, perhaps you should tell folks that you are not a stem cell scientist at all and correct me if I’m wrong, have never taken a class (let alone taught a class) on stem cell biology in your life?
First let’s get straight the answer to your question. I’ve worked in stem cell labs, taken stem cell coursework and an Atlantic Fellowship in stem cell research in the UK, worked on the NIH stem cell design program plan, led the University of Pennsylvania stem cell planning effort, was chair of the ACT ethics committee, taught incoming members of congress on legislation and stem cells, taught circuit court judges on stem cells and regulatory affairs, have written (not advised on) drafts of laws regulating stem cells in 7 states, and have authored more than 20 peer-reviewed articles, book chapters, encyclopedia entries, textbook entries, white papers, contracted advisory reports, reports to foreign law enforcement, law review articles. However, while my study of and teaching about MSCs is 100x more than you have noted in your own CV, you are correct that apart from testifying to the Senate, writing a dozen or so articles and teaching 4 classes at the University of Pennsylvania, I’ve not done much on iPS cells. Since, as you might know, I share the opinion of many of your peers that they are a political invention, and of virtually every scientist that they are (at the moment) nuclear weapons compared to MSCs. A fact you rarely acknowledge. Now granted, I left academia as an endowed full professor with tenure, and you’re working your way there. But I’m not sure I’d throw this snowball at anybody – peer or aging ex-academic – without reading a CV.
Either way I harbor you no ill will. I just think your blog is destructive to patients and research. And that this post is literally unworthy of a scientist. You should apologize and request a correction of Forbes simply on the grounds of the following:
What troubles me on reflection is that you’d cite a bogus demyelination case report as a cautionary tale in the face of huge evidence. Why? Because you didn’t read about biostatistics? Or morbidity and mortality rates? More people died per capita driving to a hospital while you read this article than have ever been discussed as having a serious adverse event in MS treatment using stem cells.
After about 5 minutes I discovered that there is a bucket of data suggesting what you do not suggest, whether it is because iPS cells show no promise of doing anything for MS anytime soon, or whether it is because you don’t use PUBMED: The reports of success of adult stem cells start really early. 2002 early. Early enough that my undergraduate intern found them in 30 seconds. So let’s look at the data of this form of stem cell intervention that you have published nothing about – and its safety issues, which you’ve also published nothing about – and its efficacy, which you’ve also published nothing about (but which somehow seems to have blossomed into an FDA PHASE III TRIAL – see http://clinicaltrials.gov/show/NCT00273364).
2002 (one patient. a number you can deal with.)
1) http://jnnp.bmj.com/content/72/1/127.long
(early…) 2011 Lancet
2) http://www.ncbi.nlm.nih.gov/pubmed/21683930
“In experimental autoimmune encephalomyelitis, intravenous injection of MSCs ameliorates clinical course and ***decreases demyelination***, immune infiltrates, and axonal loss. Surprisingly, these effects do not require full CNS engraftment by MSCs, but rely on the capacity of MSCs to inhibit pathogenic immune responses and release neuroprotective and pro-oligodendrogenic molecules favouring tissue repair. These results led to the conclusion that therapeutic use of MSCs should initially focus on individuals with multiple sclerosis and persistent inflammation. ***Small clinical studies in different neurological diseases have suggested that MSCs are safe***, paving the road for larger phase 2 studies addressing the effect of MSCs on clinical outcomes and markers of disease activity.”
2012 IMRM Salzburg
3) http://www.ncbi.nlm.nih.gov/pubmed/23283435
2012 U Genoa (Review article)
4) http://www.ncbi.nlm.nih.gov/pubmed/23124791
“An exhaustive amount of preclinical data has shown that the intravenous administration of mesenchymal stem cells (MSC), a subset of progenitor cells isolated from many mesodermal tissues, effectively ameliorates experimental autoimmune encephalomyelitis (EAE), a model of MS, through the release of anti-inflammatory and neuroprotective molecules. Based on these results, several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness.”
2012 Cell Transplantation
5) http://www.ncbi.nlm.nih.gov/pubmed/23057962
Collectively, this comparative investigation demonstrates that transplanted Ad-MSCs play a significant role in tissue repair processes by virtue of their ability to suppress inflammation coupled with their enhanced ability to home to the injured CNS. Given the access and relatively ease for harvesting adipose tissue, these data further implicate Ad-MSCs as a cell therapeutic that may be used to treat MS patients.
2012 Cleveland Clinic
6) http://www.ncbi.nlm.nih.gov/pubmed/22642335
“This article reviews the pathophysiology underlying MS, as well as providing a cutting-edge perspective into the field of MSC therapy based upon the experience of authors intrinsically involved in MS and MSC basic and translational science research.”
2013 Cleveland Clinic
7) http://www.ncbi.nlm.nih.gov/pubmed/23294498
But the thing that troubles me most, Paul, is that the case you cite is authored by a scientist whose sole interest in MS is advancing a drug called Natalizumam. Now, don’t figure that he disclosed this in his article. He didn’t. But Dr. Alderazi is the author of the most positive article about Natalizumab (brand name: TYSABRI — http://www.tysabri.com) (see: http://www.ncbi.nlm.nih.gov/pubmed/22435074 ), which (to quote NLM Medline+) “may increase the risk that you will develop progressive multifocal leukoencephalopathy (PML; a rare infection of the brain that cannot be treated, prevented, or cured and that usually causes death or severe disability).”
Here’s the wrinkle, Paul. TYSABRI is owned by Elan pharmaceuticals. No big deal right? Also, we know that Dr. Alderazi has no conflicts of interest, because it says so in his self-disclosure in the American Academy of Neurology annual meeting for 2013 (http://www.aan.com/annualmeeting/search/?fuseaction=disclosures.home&letter=A&lastname=&start=1039&p=781 ). Surely then it is an accident that “NewsRX.com,” an industry “market analysis” circular, put Dr. Alderazi’s case study out in a press release of “Key statistics on the Pathology Industry”? (http://www.reportlinker-news.com/n040389012-article/Findings-in-Multiple-Sclerosis-Reported-from-St-Joseph-s-Hospital.html) That 5 people have ever cited the article you find so interesting, when more than 50 have cited safety /studies/, and that the acute induction is regularly reported in young MS patients anyway (http://www.ncbi.nlm.nih.gov/pubmed/11099444), would seem to be irrelevant. But do you find it even *slightly* interesting that Elan Pharma paid to make sure you’d see what the one commentator described as “the single reported case in the history of MSC use.” Ask the patients who agree with today’s Nature Editorial recommending that the FDA allow compassionate exemption for them when there is no option left whether or not they think they should be able to take those odds, you know, the ones that compare favorably to driving to a hospital in Houston.
I think that it is a disservice to your readers to represent that this case belongs in a blog post that purports to list three things people “need to know about” if they think stem cell interventions are risk free. Unless of course you will also caution them that driving to stem cell interventions is a significant risk.
Glenn,
I don’t see anything wrong in bringing these cases to public discussion. Nobody does it, but these cases are exist and we have to critically evaluate them. The main trend in mass media and in professional online networks is discussion of “adult stem cell success and miracle”. I think it makes the field and public expectations over-hyped. But, so far, there is no basis for such hype. No trials ended with conclusive evidence for efficacy so far (here in US).
I’d support Paul in his intention to bring these cases and papers to public discussion. The only thing, I’d add that we can not draw far-reaching conclusions for public about the safety based on these reports. But still, these cases must be taken in account and cited among professionals.
How many times you have hear on conferences about excellent safety profile of adult stem cell therapies? Hundreds? Nobody ever mention these cases as anecdotes which possible link to cells. There are more cases, which usually never been discussed.
I was trying to discuss them and critically evaluate with professionals on my blog, but didn’t get any comments. So i was not able to spark any discussion.
http://celltrials.info/2012/11/18/severe-acute-neuroimmune-complications-adult-stem-cell-therapy-analysis-2-cases/
Well, at least we have something now going on here.
All papers that you’ve listed also should be critically evaluated and discussed among professionals. Many studies and trials that you’ve cited are inconclusive (ex: POSEIDON) for efficacy, although confirm good safety profile.
I think, Instead of shooting each other by papers, digged from PubMed, we should take each of these cases/ publications and critically evaluate and discuss with professionals. That’s what I’m trying to do on celltrials.info
Alexey,
Thank you for your post. It is refreshing that you consistently remain committed to public dialog without descending into ad hominem. I hope that you would agree that in this post alone, the level of ad hominem allowed by the blogger reaches an astonishing level.
Let’s stay at the level of scholarship and discussion. I agree completely that anecdotes must be analyzed, alongside the many many published studies. I do also believe that a study does not have to be published by Americans to be valid, however, and the continuing claims that articles published in ISI ranked journals that are “Asian” is bad science at best and can even be racist.
In any event, these are the issues I wanted to address, and to which you respond directly:
1) when a blog post purporting to help patients raises 3 dire concerns, and one (which results in a Forbes article) is the resurfacing of a case study previously cited 5 times (in a literature where case studies are often cited dozens of times). It is of interest to the public – who are the intended readers of this blog and of Knoepler’s quotes in Forbes – that this is the only study EVER published to show any such side effects. It is unthinkable that the blogger failed to do enough checking to determine that the case report is authored by a physician who happens to be funded by and publishes about the wonders of a competitive medication (with a common, horrifying side effect profile – particularly by comparison using ANY form of data analysis). Again one would expect that Paul would revise the post.
When made aware of both the source’s issues and of the fact that in precisely this patient population, this event is a well-known MS symptom anyway, we can agree can’t we that Paul would owe the public – who otherwise might have no idea – that these three issues constitute a significant failure and probably scientific misconduct, and that the total number of people who have treated this case as being of importance = 5, though more than 30 articles on safety in stem cells and MS have been published in the past 3 years.
I think it is possible to acknowledge the value of the anecdote but that the rules of reporting case studies are pretty well understood and that Paul’s one limitation on his report of this Costa Rican nightmare was worse than impoverished (‘it’s only an n of 1’) because it is written for a public whom he asks to trust him about risks. If you think this study constitutes reason to fear stem-cell induced demyelination, then you and I do disagree about public science. I believe whole heartedly that stem cell exceptionalism (a term I gladl
…sorry…hit return accidentally…
…gladly own up to coining, is as dangerous whether positive or negative and that both Forbes and this blog should be amended. I believe Paul will take that step. If he doesn’t, then I for one will not be commenting for the public here.
You make a final comment that troubles me. “I think, Instead of shooting each other by papers, digged from PubMed, we should take each of these cases/ publications and critically evaluate and discuss with professionals. That’s what I’m trying to do on celltrials.info”
Do you really think that the problem in discussion of cell therapy is in providing the public with access to vetted studies so that they can look to make their own decisions? If so, are you seriously suggesting that from the premise “anecdotes matter” comes the conclusion “so don’t offer up data?” It seems to me that if you are going to say something to the effect that there has been no demonstrated efficacy in stem cells to date, it matters quite a bit that the studies I cited, at least, draw the conclusions that they do. And as a human being, with a father who has parkinsons and a wife who has graves, I’d like to be provided a lot more information than the scare tactics in this post. Nothing demonstrates better how serious is the responsibility of the stem cell expert than the speed with which this thing went from blog to Forbes. You are wrong that the media treats adult stem cells as nothing but miracles. The vast majority of “toss off” articles in English language about MSCs are profoundly negative. No risk goes uncovered. What is in absence is any philosophical debate about risk analysis for incurable diseases.
Whether we agree or disagree I respect your argument and the post you reference was helpful.
Glenn,
Your experience in stem cell policy is impressive. And I did not know you worked in an actual stem cell lab–which lab was that? Also what stem cell course(s) did you take? Cell biology? Biochemistry? Molecular Biology?
I’m surprised you don’t mention your time as President of Celltex (see PR almost exactly one year ago: http://www.prnewswire.com/news-releases/celltex-announces-glenn-mcgee-phd-as-president-of-ethics-and-strategic-initiatives-139217394.html ) or your current job as CEO of RNL Europe. It seems like these are important experiences too.
In terms of iPS cells, I am in fact an advocate of caution in terms of their clinical use (read my blog!) as much as I am excited about the cells. Recall Yamanaka did win the Nobel Prize.
Paul, thank you so much. There is great value in providing the patients with accurate studies. Clearly, scientific interpretation of a study should never be left soley in the hands of patients with no medical knowledge. Having access to a scientist who will interpret, evaluate and check validity is invaluable. Of course we want to know the good as well as the bad. So many of us in the MS Community have spent countless hours sharing with one another and sifting through information trying to differentiate between the types of cell therapy available, and what is involved in cell manipulation. We know just enough to be dangerous! Ha! Thank you for stepping up and giving us some studies to look at. I know you did a blog spot on questions to ask in considering cell therapy. The questions you posed could potentially save a patients from a dangerous situation. If you can produce more studies showing pro’s and con’s of cell therapy, here and abroad, that would be most helpful. When we asked you to engage with us, this is exactly what we were referring to! Thank you!