For this Friday afternoon I thought I’d rehash a previous post from denialism.com on adult stem cells and those that hype results inappropriately to disparage embryonic stem (ES) cells. It all started with an exciting JAMA article about using autologous stem cell transplants to help treat type I diabetics who still had some capacity to produce insulin. The problem is that the adult stem cell hypers, like Wesley Smith (you guys remember him right? Senior fellow of DI etc.) will jump on any article that says “adult stem cells” and blather on and on about there are no ES cell cures – so why study them?
See, the thing is about 5 years ago, there were a bunch of papers about adult stem cells, some neural, some hematopoietic, some derived in other ways, and their varying ability to transdifferentiate. That means to change from one cell type into another. Stem cells can of course differentiate into the progenitor cells that they are identified as replenishing in the body and this has been known for decades. A single hematopoietic or blood stem cell can, for instance, replenish the body’s entire blood supply, this is known and has been involved in treatments for decades. However transdifferentiation is when those stem cells get tricked into making a cell they wouldn’t ordinarily make based on the idea that stem cells are generally plastic. These papers were very cool, there were even some in our field in which they purported to show that up to 70% of smooth muscle cells in lesions generated in blood vessels induced by various methods were blood stem cells that had transdifferentiated into a smooth muscle phenotype. It was one of those moments in science when an idea was hot and lots of people were rushing to publish on it.
Now, this is why I wish everyone would watch the lecture from Ioannidis on how scientific publication often goes through swings of exaggerated findings that are eventually brought down to Earth. It happened in this case, Nature published two papers on stem cell fusion, quite unapologetically I might add, that seemed to indicate that many of the findings (some of which had been published in their own journal) might not have been real. Instead the cells only appeared to have transdifferentiated but in reality had only fused, or essentially stuck, to another cell giving the appearance of differentiation when there really was none.
Ouch. Suddenly everyone is attuned to adult stem cell fusion, lots of papers are being looked at more carefully, and many results, when subjected to higher resolution methods, were far more modest or (including that one in our field) simply fell apart. All those old papers are still part of the literature, and only someone who’s been watching the story unfold will understand that, taken out of context, the literature gives a completely different picture of the so-called plasticity of adult stem cells.
Then enter a political problem. George Bush doesn’t want human embryonic stem cells studied. Human ES cells, are taken from the inner cell mass of a pre-implantation embryo that’s little more than a ball of a hundred or so cells. These cells were isolated in mice in 1980, but it took another 18 years before the same feat could be replicated in humans (this time difference becomes important). It also can not be emphasized enough, ES cells are the real deal. By definition, they are capable of differentiating into every cell in the body (I work with they mousey-type), and you don’t even need to work really hard to make them differentiate, all you have to do is aggregate them or remove the chemical signals that you use (a chemical called LIF in combination with a feeder layer of embryonic fibroblasts – although new methods are in place) to keep the cells from spontaneously differentiating. They make everything. This means they have enormous potential for tissue engineering as well as for in vitro study of development and differentiation.
Take for example this little video I made of a cardiac “beater” in one of my embryoid body differentiation cultures.
That’s spontaneous cardiac contraction from cells derived from ES cells. These cardiac foci are a good example of the power of ES cells, cardiac stem cell populations are small and difficult to isolate and adult stem cells isolated from fat or marrow probably won’t form myocytes, or only at very low frequency (if at all probably through fusion). In fact the stem cell injection protocols for treatment of myocardial infarction might not be benefiting from differentiation so much as formation of fibroblasts, secreted factors, etc.
Well, you can see that for those who don’t want these cells used their ability to spontaneously make cells from all tissue types is a disaster. Clearly there must be an alternative! Enter, adult stem cell hype. One of the reasons I include this as denialist crankery is because of some of the perpetrators. Wesley Smith a co-founder of the DI is constantly harping on how adult stem cells are hitting the market while ES cells? Nothing. Never mind actually reading what kind of treatment that was, essentially a piece of total quackery in which they include the magic adult stem cells in a fat-transfer breast augmentation. Not exactly the kind of result one should try to hang their hat on to prove their point but Smith has such a poor understanding of science he’s perfectly happy to describe propranolol as “Soma”. All-purpose crank Michael Fumento loves writing about it too, with articles essentially saying ES cell research is a scam (Hwang Woo Suk is apparently proof every scientist in the field is a liar), and adult stem cells can do everything. Sites like Do no harm publish lists of adult stem cell successes, which basically represents a pubmed search and a cut-and-paste of anything that even mentions an adult stem cell, and most references on closer inspection are a joke in terms of demonstrating adult stem cell plasticity. You hear arguments that ES cells haven’t resulted in treatments even though they were discovered 30 years ago! Because they weren’t, they were discovered in humans less than 10 years ago. Even Anne Coulter cribbed a list of “adult stem cell cures” for her latest book. And every time there is a new result in which adult stem cells are used they go nuts. The latest from Wesley Smith hyping adult stem cells is this Jama article, “Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus”. An anon in my comments also asked what I thought about this as, I guess, proof of adult stem cell therapies. My response is that this is not even relevant to the discussion. This is the problem with the hyper, they don’t care about the meaning of the science. This paper is not about transdifferentiation potential of adult stem cells, which has largely been discredited. That’s not to say there hasn’t been some wonderful progress, in particular in reprogramming adult stem cells and in spermatogonial stem cells which both act very ES-cell like, but have yet to be fully characterized.
But that’s not enough for a crank. There is real progress in these fields but a crank can’t just be satisfied with modest progress and some signs of advances. They have to make every adult stem cell paper out to be a godsend, and all ES cell research, and the researchers, demonic liars who are perpetuating some kind of hoax. Creeps like Krauthammer (creep or crank? probably both), suggest stem cell research is so fundamentally corrupting it makes scientists evil while hyping their modest advances.
This most recent paper is a good example. One, this is not a “cure” for type I diabetes. The follow up is only a mean of 18 months, not all the patients were able to go insulin free, and frankly if this were my kid I wouldn’t give them this treatment, it’s extremely dangerous – I’ll explain at the end. Further, the real distraction here, is that this has little or nothing to do with transdifferentiation which is the real dispute between the adult stem cell and ES cell advocates. These cells aren’t transdifferentiating in some special way, they’re doing what hematopoietic cells always have done, make blood. This is not a stem cell breakthrough, this is a immune-system reprogramming breakthrough.
What this paper is really showing is that if you whack an emerging diabetic’s immune system with a hammer, and then re-establish it with hematopoietic stem cells from the same patient (that you saved in the freezer from before you started), you have some ability to short-circuit the body’s attack on the insulin-producing beta cells of the pancreas without permanently destroying the patient’s immune system. Very interesting stuff. Nothing to do with adult stem cells vs ES cells, but hey, they’re cranks, they don’t really care about science.
The debate is about which cell type can transdifferentiate into cells of any kind. There is limited evidence of the potential of adult stem cells to transdifferentiate. Everybody knows a hematopoietic stem cell can differentiate into blood, so this JAMA study doesn’t say what they think it says. The cells aren’t transdifferentiating and making islet cells which is the implication from the hyper, they’re making blood cells, and this treatment would only work for diabetics who are just beginning to become insulin dependent, not those who have already lost their islet cells. Embryonic stem cells, by definition, differentiate into every single cell type in the body, it’s just what they do. They make islet cells, albeit at low frequencies, but that’s a technical problem, and real science moves pretty slowly.
As a post script I’d say, this is also a treatment in its infancy. The study is also missing a valid control group (it probably would have been unethical), and is not some minor intervention. This would be a very dangerous treatment to undergo, and would have to be done at major medical centers since it involves temporary destruction of the patient’s ability to fight off illnesses. Such a treatment could take a kid and make him insulin independent for 18 months, but it could easily kill the patient who would otherwise have lived a normal, if insulin-dependent, life. Further, I will mock, endlessly, magic-bullet type ES cell treatments which are also based on bad science and have the potential to really damage the field.