As scientists await Obama reauthorizing federal funding of embryonic stem cell research and the FDA approves the first clinical trials using embryonic stem cell treatments, there is an important case report that highlights the potential safety issues with putting stem cells in humans.
Amariglio et al. report a case in PLoS Medicine of a boy treated by spinal injections of fetal-derived stem cells for a developmental disorder called ataxia telangiectasia. Four years after treatment, the boy developed brain tumors.
From the abstract:
A boy with ataxia telangiectasia (AT) was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA) typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors.
I am sad that I was right. One of my criticisms of "stem cell tourists" -- patients traveling to China for injections of stem cells that are not approved treatments in the US -- was the cancer risk. This case study confirms that concern is a reasonable one.
We don't know in what contexts stem cell treatment will be clinically effective, and considering the risk of cancer -- stem cells are dedifferentiated and hence are very much like cancer cells -- we shouldn't be using them willy-nilly. Despite the huge optimism out there, these treatments need to go through the same process of rigorous clinical trials that we expect of other types of treatments.
Unfortunately that process is likely to be a long one, and I would expect that cases of stem cell-induced tumors will become more common in the coming years. It may turn out the primary downside for these treatments is an elevated cancer risk.
The implication here is that stem cells are not a silver bullet curing all ills. They will have to be used sparingly, weighing costs and benefits, just like every other thing that doctors prescribe.
Hat-tip: Wired Science
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I have just finished my PhD in brain tumour genetics in the UK and stumbled across your interesting blog.
It's indeed sad, and a very sobering reminder that we need to temper our optimism with hard science.
We certainly have to understand a lot more about the basic regulation and developmental pathways of neural stem cells before we use them for clinical therapy. It's extremely concerning that a lot of unlicensed clinics around the world are profiteering from this, giving patients false hope of a cure. Stem cell therapy still holds great promise, but right now they are too powerful to just inject like that. Essentially these patients are guinea pigs. I remember the case of the boy treated with gene therapy who developed cancer because the gene inserted and activated a proto-oncogene. It amazes me that we can go ahead with such experiments despite having no or little control of what happens once the experiment goes ahead. NSCs are multipotent, and as you said, dedifferentiated, being akin to cancer cells.
This story does give credence to the cancer stem cell hypothesis though, at least in the brain.
So, what's the ETA on the first poorly informed; but deeply sanctimonous, article in the "We tried to tell you this would happen; but you were too busy playin god and killing baby fetuses to notice. *oh morally superior woe*" vein?
Lets make this clear.
What were used were fetal stem cells and not embryonic stem cells. No knowledgeable researcher advocates injecting undifferentiated embryonic stem cells, but embryonic stem cells that have irreversibly entered the differentiation pathway that will produce the therapeutic cells desired.
It was a sloppy, criminal job of injecting a mixed jumble of fetal cells, some of which were neural in nature, and apparently some non neural.
The purity of the injected material caused this problem. And lets not describe it as a cancer, since as far as I can see it was not metastatic. The cells stayed within the nervous system, probably where they had first engrafted.
What the FDA in the US has just approved for a phase 1 trial in spinal chord repair by Geron Corporation are embryonic stem cell derived oligodendrocytes that have proven their purity in hundreds of test animals supported by more than 22,000 pages of test data. The largest IND submittal ever received by the FDA.
The general public has such a poor undertanding of the terminology of the new science of regenerative medicine using cells derived from embryos that articles like this only give fuel to the religious extremists who are trying to block its development.
Let me first state that I am fully in favor with advancing stem cell research. But the very idea of attacking an apparently factual article because someone might misuse it to criticize or attack the field? That borders on hiding data because you don't like the implications. I'm sure that wasn't your intent and you are just anticipating the upcoming quote mining and misinterpretation this article is probably going to suffer.
"Jake Young is a MD/PhD student at Mount Sinai School of Medicine focusing in Neuroscience. He is due to graduate in 2032. He received a BS and a MS in Biological Sciences from Stanford University -- where he spent most of his time drinking heavily and building vegetable catapults instead of learning information that would now be eminently useful. When he is not failing terrifically to perform his sworn duties, he enjoys watching bad movies, ethnic food, and running."
It says it all, don't it?
There are several reasons that the infection rate might be different after nonmyeloablative or reduced toxicity regimens compared with standard regimens of transplantation.
Increased support for stem cell research is a great idea. But simply injecting cells into people and assuming the procedure will cure a variety of illnesses does NOT constitute research. Without proper controls and preliminary testing, it's a risky, expensive fishing expedition that merely collects anecdotes. And as the old saying goes, "The plural of 'anecdote' is not 'data'."
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