Stroke story stem cell hype analysis: 9 very different headlines

I wrote yesterday about two cases of science media hype on CRISPR and on stem cells for strokes. The latter case on stem cell hype stirred the most discussion and even some harsh words in the comments.

As this stem cell stroke story on an encouraging but very small, preliminary study has unfolded across the mainstream and other media in the past 24 hours, a whole range of headlines for it have popped up. I’ve got a screenshot of a Google result for this story below with 9 headlines all related to the same science. I find it interesting how variable the headlines are.

stem cells stroke hypeSome are reasonable such as the one on Bradley Fikes piece at the San Diego Union Tribune, although to nit pick I would have added the word “small” to describe the study. Again it is generally editors and not writers who pick the titles.

On the other end the worst I’ve seen so far, outpacing the hyped headline in the Washington Post, comes to us from a usual hype suspect, The Daily Mail: “Stroke patients to work, talk, and live a normal life after stem cell treatment”. This irresponsibly suggests a cure for all patients.

Keep in mind again this was a very small and preliminary study. If it holds up and clear benefit and safety are proven in a large trial then some (but not all) of these headlines could be more reasonable.  One might think from the headlines above that this was a large Phase III study or something like that.

The science behind this study seems rigorous and the early results encouraging, but caution is needed in media coverage so as to not mislead patients or generate oversized expectations that may never be met.

16 thoughts on “Stroke story stem cell hype analysis: 9 very different headlines


  1. Paul ,
    You are right about the hype …….The things I find interesting was the Bone Marrow MSC injected into these patient where directly to the site in the brain that was effected ….Never done before as far as I know …..Now understand that adult MSC stem cells do not migrate very well, which is a good thing ……so you do not get rolling, triggering, adhesion and diapedesis , the process by which embryonic stem cell migrate across the enothelium such as brain tissue, especially the CNS in the brain for stroke or Parkinson disease…….We have been told by Robert Lanza from his work that embryonic MSC stem cells migrate much better than adult derived stem cells ….. in his papers ……Much to be done on how MSC effects CD4 T reg pathways at the microbiome environment …..

    Andy


  2. Inaccurate media reporting of science advances has been a problem for as long as there have been advances and media to report them. What has gotten worse in recent years is the way inaccurate reporting is repeated to an even wider audience via twitter.

    Case in point: In March a clinical trial began in Australia using sibling cord blood for cerebral palsy. This was reported in the Sydney Herald newspaper with the headline: “Children to receive umbilical cord blood in world first cerebral palsy trial”

    This was widely rebroadcast on twitter by people who should know better. The only thing about this trial that is a world’s first is that it is in Australia.


  3. MSCs (and NSCs) are not all the same. Some preparations migrate more than others, and their migratory behavior can change after they’ve been expanded in culture and if there’s a change in the way they’re cultured. They change in other ways, too.

    I know I’m up on my soapbox again, but we must develop assays that define the cells that are used for transplantation- not just immunocytochemistry, flow cytometry, and karyotype, but also gene expression profiles, genome sequence, SNP genotyping, and metabolic assays if warranted.

    I would love for the FDA to enforce these quality control measures, but we should be doing them anyway.

    These profiles can be correlated with the behavior of the cells and the clinical outcome. This is the only way that we’ll ever figure out how to make effective cells for each application.


  4. @Paul,

    While this was a small stroke trial of 18 patients the results were encouraging. Moreover, no one mentioned here or in the previous blog post that this is not the only evidence that allogeneic adult stem cells can help stroke patients. Last year, Athersys reported 90 Day post-hoc stroke analysis that were also encouraging but initially met by skepticism on Wall Street. However, earlier this year they reported 1 year follow-up data that actually met statistical significance for efficacy in the same measurement that lead to the approval of tPA about 20 years ago, still the only approved drug for stroke. Interestingly, the more time that passed, the greater the efficacy distance between the treated group and the control group. The Athersys trial, of about 120 patients, was double blinded and placebo controlled and the allogeneic cells were administered via IV on ACUTE stroke patients. So it seems pretty convincing that the cells have a long term effect by sending signals to resident progenitor cells in the damaged area to begin making repairs. We know that the adult stem cells used in both studies are removed from the body after they do their work and do not engraft. So while Stanford injected cells directly into the cranium on chronic stroke patients and Athersys treated ACUTE patients within 48 hours of onset, I think it is fair to say that 1 + 1 = 3 here as both studies should be considered confirmatory to each other with regard to longer term angiogenesis and neurogenesis potential that is evident in these two studies. So while you focus on the hype, Paul, I’ll go out on a limb and say there is something here in stem cell stroke therapies and the preponderance of evidence is strengthening.

    For those interested in reading about the Athersys stroke trial and its Japanese stroke partner Healios, I invite you to read my recent article: http://seekingalpha.com/article/3968415-stem-cell-company-athersys-firing-cylinders-2016

    P.S. Paul, there is a problem with your website using chrome when you try to post a long comment. The “post comment” button disappears.


    • @WSTR – you say “..cells have a long term effect by sending signals to resident progenitor cells in the damaged area to begin making repairs” – is this speculation based on the long-term effects after removal of the stem cells or is there any real evidence for activation of resident stem cells by the MSCs. How could this activity be maintained after MSCs are removed?


      • @Jeff Muggles

        I will quote the explanation from Gil Van Bokkelen in the article I linked to regarding your question, “How could this activity be maintained after MSCs are removed?”

        “Furthermore, the preclinical data from studies where we examine gene expression in the brain following treatment shows that we stimulate the repair process by upregulating a number of factors and processes linked to healing and recovery. Although we can’t harvest brain tissue and do that same experiment in human subjects, the clinical results are certainly consistent with those observations. So in essence, treatment with MultiStem has multiple benefits, and creates an environment that is more conducive to repair and recovery, which occurs over time. Although this was certainly evident in some respects by the recovery at 90 days, especially among the patients that received treatment within 36 hours, it seems clear that a meaningful number of patients treated with MultiStem continued to improve over time, which is very exciting.”

        Although MSC and progenitor MSC like cells don’t engraft, recent research has demonstrated that they excrete extracellular vesicles as the signaling messengers that communicate with the local niche as miniature drug depots . This fascinating German study hits the nail on the head in answering your question(http://stemcellstm.alphamedpress.org/content/early/2015/08/31/sctm.2015-0078.full.pdf+html). @Paul I hope you give it a read and give your expert opinion, not about all the hype in the media, anyone can do that, but about the overall evidence that IMHO strongly suggest a therapeutic benefit in stroke with allogeneic adult stem cells.

        Here is the summary of the German study:

        “Transplantation of mesenchymal stem cells (MSCs) offers an interesting adjuvant approach next to thrombolysis for treatment of ischemic stroke. However, MSCs are not integrated into residing neural networks but act indirectly, inducing neuroprotection and promoting neuroregeneration. although the mechanisms by which MSCs act are still elusive, recent evidence has suggested that extracellular vesicles (EVs) might be responsible for MSC-induced effects under physiological and pathological conditions. The present study has demonstrated that EVs are not inferior to MSCs in a rodent stroke model. EVs induce long-term neuroprotection, promote neuroregeneration and neurological recovery, and modulate peripheral post-stroke immune responses. Also, because EVs are well-tolerated in humans, as previously reported, the administration of EVs under clinical settings might set the path for a novel and innovative therapeutic stroke concept without the putative side effects attached to stem cell transplantation.”

        WST


        • @WST – many thanks, interesting to see some preclinical mechanistic data. The MSC EV story would be a paradigm shift in cell therapy if it can reproduce the effect of whole MSCs, as we then have a non-replicative cell-derived therapy, which may reduce safety concerns, increase patient coverage and lower costs. How such long-term potentiation works for MSCs and EVs will be interesting as it points to some form of in situ reactivation of adult stem cells or progenitors – the holy grail in stem cell therapeutics.

          In this framework, there are compelling studies showing that neurogenesis in the hippocampus can be induced by exercise and modulated by the immune system, so maybe we’re closing in on the mechanism and can develop more specific therapeutics.


  5. @WST, this is a good point on other encouraging stem cell stroke data.
    Sorry on the comment length issue. I’m trying to resolve, but so far no luck.
    Paul


  6. For everyone with the comment length issue, hit your keyboard’s tab key a couple times while in the “Leave a Reply” section. This makes the box “scroll down” and you should be able to see the “Post Comment” button.

    I second Jeanne’s approach. The stem cell field in particular seems to have little knowledge in general of how to properly characterize cells for either purified preparations or heterogeneous compositions. There is an especially egregious lack of understanding of how to correctly design, carry out, and analyze FACS experiments and gene expression analyses (even for microarrays! In 2016!). There is still a lab in the muscle cell therapy field that relies on getting their cells of interest from a ridiculous series of preplatings and has never carried out a serious characterization of what cells are falling out and what the end result is.

    The major problem is that the most egregious offenders of this are some of the very big names in the field, so I don’t have much hope for it changing without intense pressure on the NIH/FDA.

    Also further echoing Jeanne’s MSC comments, there was an idea being floated a few years ago that adipose-derived MSCs could be differentiated into bone, fat, or muscle. For bone, it turned out one could only get a specific type of osteogenic cell (without extensive and expensive culture condition manipulation). Fat, of course no problem. Muscle, despite many people claiming it could be done, I never saw any convincing evidence that it worked. All of this goes to the point that source tissue may matter, too.

    Also, I seem to remember from a few years ago that CIRM wasn’t particularly interested GMP-level characterization and validation of transplantable cells; they were only interested in “gud enuff.” Hopefully, this has changed?


  7. I’m planning an update post on the science of stem cells for stroke in the coming weeks. Stay tuned. Paul


  8. This is from Stanford Health Care’s Twitter Feed.

    Stanford Health Care ‏@StanfordHealth 23h23 hours ago

    #StemCells allowing #stroke patients to suddenly walk again, according to .@StanfordHealth’s Gary Steinberg, MD http://stan.md/1r5Owwa

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