Does stem cell clinic IRB approval mean much? Insights from blinding cases

Could the blinding of three women at a stem cell clinic have been prevented by better oversight or was the clinic acting outside of the scope of oversight by its institutional review board (IRB)?

More broadly, when is an IRB conducting proper oversight and how do we know? When on the other hand is it not being careful enough or even outright enabling risky behavior by those selling non-FDA-approved, experimental stem cell “treatments”?

It can be hard to really be sure. What makes this area particularly muddled is that most of what IRBs do is confidential. We in the stem cell community are as a result left with a bunch of questions in general and about specific cases such as the blinding of these women.

When things go wrong and patients have bad outcomes how much is the responsibility of an IRB versus the stem cell clinics doing the actual experiments? Stem cell clinics often point to their IRB-approved status as some kind of merit badge, but how much does that approval mean? My goal in today’s post is to tackle that last question.

stem cells eyes

Kuriyan, et al. 2017 NEJM Figure 2A showing patient with severely damaged eyes leading to loss of sight

Over at BuzzFeed reporter Peter Aldhous has been following the story of the three women who were blinded by experimental offerings of US Stem Cell, Inc. In Aldhous’ new article he focuses more on US Stem Cell’s IRB. This IRB was run by an organization called the International Cellular Medicine Society (ICMS), which in theory was responsible for overseeing work of US Stem Cell.

There are a host of questions about what happened leading to the women losing their vision and what if any role the ICMS IRB had in overseeing the experiments on these patients. Did US Stem Cell wander outside the scope of ICMS IRB oversight in this case? Could the ICMS IRB have done a better job? If the ICMS IRB did its job well here, I still wonder how they can help to prevent more bad outcomes like this from happening? Presumably the ICMS IRB is overseeing work by many other stem cell clinics as well. How much risk is there at those places? If a business doesn’t follow its IRB’s rules, what happens then? It’s hard to find answers to questions like these. Continue reading

A tale of two stem cell retractions: stark contrast between Macchiarini & Egli

A paper retraction is a major, painful step in science, but sometimes it is necessary and in the past few weeks we’ve seen news of two high-profile stem cell paper retractions. However, these retractions were handled entirely differently by those involved and were prompted by very distinct situations. Update: for some background on stem cell manuscript retractions more generally see from Retraction Watch here and from this blog here.

In the case of a JCI stem cell manuscript retracted by Dieter Egli’s lab, a central problem was with the cells used in the study. The IPS cells had major genomic abnormalities it turned out, prompting the retraction. Senior author Egli and first author Hailing Hua agreed to the retraction due to this problem and due to the fact that after Hua left Egli’s lab, the lab was unable to reproduce the results reported in the paper. As difficult as any retraction is, it seems like Egli handled it far better than most groups do.

Macchiarini retraction

In the second stem cell paper retraction case, we see quite a contrast to the first. Here we have former “star” surgeon Paolo Macchiarini retracting a paper from Nature Communications entitled “Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats”. Retraction Watch has been on this case for some time and done a lot of other reporting on Macchiarini’s travails that involve investigations of other papers too. The Karolinska Institute (KI) dismissed Macchiarini amid accusations of misconduct. Continue reading

The Real Stem Cells of Beverly Hills?

They say a picture is worth a thousand words and with stem cell clinics and GoogleMaps, maybe it’s true.

When Leigh Turner and I published our stem cell clinic paper in Cell Stem Cell last year, Beverly Hills stood out as a top hot spot for these businesses selling non-FDA approved stem cells.

Beverly Hills Stem Cells

GoogleMaps results from “Stem Cells Beverly Hills” search

See the GoogleMap image from a search today above with the search terms, “Stem cells Beverly Hills”. According to GoogleMaps, just drive down Wilshire Boulevard through Beverly Hills and you could sample many of the stem cell businesses, some of which are just blocks from one another.

It’s like the stem cell direct-to-consumer epicenter of the universe.  

I’m not saying that everything or everyone listed in this map from GoogleMaps is a stem cell clinic, but many are. I recognize almost all of these entities, but I don’t recall Jian N. Ye as a stem cell provider.

There are so many entities on this map that Google couldn’t fit the names of all of them in there. There are also some others off the edge of this particular map but nearby. Continue reading

On St. Patrick’s Day, an update on stem cells in Ireland by Stephen Sullivan

Happy St. Patrick’s Day from the Irish Stem Cell Foundation (www.stemcell.ie)! I’ve included a few picture from the parade here in Ireland.

St. Patrick's Day Parade Ireland MusicianScientifically, Ireland is going through a lean period. The national science funding agency SFI is having its first grant call in 2 years. If recent history is a predictor, they are more likely to fund grants based on geography (which centre or college you are associated with) and how quick the perceived economic benefit will be. This means information technology (particularly areas like Fin Tech) are a lot more likely to get funded than long term pursuits like biomedical research. It is not surprising then that we see the national centre for regenerative medicine research (REMEDI) being subsumed by the centre for medical devices (CURAM) as there has been little evidence of an immediate economic return.

This move may actually might be a good thing for stem cell research in Ireland, as the centre has had a near monopoly of national funding for the last ten years or so, meaning if you were not a researcher at the centre, you weren’t likely to get stem cell work funded. There are researchers with stem cell expertise in other colleges and centres now who might be supported in the future. So we shall wait and see what happens.

St. Patrick's Day Parade Ireland Politically speaking, science is weaker in Ireland now than at any point in the last twenty years, Ireland has lost its national council for bioethics, its independent office of Chief Scientific Advisor (the public servant charged with dispersing Ireland’s investment into science, is now also charged with assessing its impact – an obvious conflict of interest). Worse again, we have no Government minister with Science mentioned explicitly in their brief. So as North American scientists mobilise against denial of Science in public policy or proposed funding cuts, it’s something we have struggled with in Ireland for some time.

Despite the climate, Irish stem cell researchers have to fight against misinformation peddled by scammers and the zealous. A recent discussion I partook in at the BBC shows the particular problems we face in Ireland with regard to stem cell research, often it with get rolled in with a lot of ancillary topics that the Irish Government has also not dealt with. Thus, it is our job to extricate all the different topics and show where the status of each truly lies.

The short discussion included topics as diverse as stem cell tourism, reproductive cloning, artificial embryos, embryonic- and induced pluripotent- stem cells, 3 parent IVF, IVF embryo storage, artificial wombs, and the history of ‘fake news’ in cloning: Dolly the sheep ‘eating shepards’, and stem cell derived-sperm and eggs.

Hard work and slow progress.

You can listen to it by clicking here and scrolling in 34 minutes into the program where our discussion starts. Feel free to tell us what you think at @irishstemcell on Twitter or via email info@stemcell.ie.

Stephen Sullivan PhD, CSO Irish Stem Cell Foundation

Takahashi team IPS cell vision paper marks major stem cell milestone

Ring the bell for a stem cell milestone.

There’s been a whole lot of commotion about the NEJM article yesterday documenting the experiences of three women with macular degeneration who were blinded by non-FDA approved stem cell eye injections of fat stem cells at a business in Florida, but in the same issue of the journal there also was some encouraging stem cell news that came in the form of essentially a mirror image of the bad news paper. We can call it the “stem cell good news-bad news” issue of NEJM.

Takahashi IPS transplant

Mandai, et al. NEJM 2017 Figure 1C

The good news was the publication of the first paper on clinical use of IPS cell-derivatives in a human patient. A big milestone. This groundbreaking manuscript comes from the pioneering team in Japan led by stem cell scholar Dr. Masayo Takahashi. I’ve written extensively in the past about the work of Takahashi and her team with IPS cells, and she received my Stem Cell Person of the Year Award back in 2014.

In the new paper they detail their data from the clinical study using sheets of retinal pigmented epithelial cells (RPEs) made from IPS cells in this case derived from the patient herself for autologous use. Remarkably in Figure 1C (above) you can see the actual transplanted RPE sheet in the eye of the patient (see dark area indicated by white arrow). The most encouraging part of this study was that the patient’s vision remained stable (rather than declining as expected) following the treatment. Was that due to the transplant? We can’t be sure.

Also, this is just a beginning as it is just one patient, but it is very exciting and represents a big milestone for the IPS cell and broader stem cell field, providing real hope for patients with vision loss along with parallel ESC-based clinical trial work as well.

This paper contrasts so much with the report from the other one in the same issue on the terrible outcomes from the stem cell clinic’s use of fat stem cells in the eye. While the use of fat stem cells themselves is highly questionable in my view for this application, the biggest differences between the two approaches is that the Takahashi team work was extremely rigorous, careful, based on extensive preclinical studies, had governmental approval, and was in essence science-based clinical medicine.

For instance, the Takahashi team was appropriately cautious with Patient 2 since the cells exhibited some genomic changes. At least in part for that reason, moving forward this clinical work will primarily focus on allogeneic use of IPS cells via an IPS cell bank being developed by Shinya Yamanaka.

We can also look to other future IPS cell-based trials coming on-line including for Parkinson’s Disease and other conditions, which are likely to be allogeneic as well in Japan, but probably autologous here in the U.S.

I love a good stem cell milestone!