The amount of basic research on stem cells has grown almost exponentially, and some clinical trials are underway. While most of the public has been fairly well informed about the controversial but seemingly endless (and sometimes overhyped) potential of embryonic stem cells, insight into the surprising level of activity of adult stem cells in the body and their therapeutic possibilities is less well known.
Stem cells can be described as being healthy young recruits into the Army who have completed the basic training phase of their careers, but who are as yet unassigned to any military specialty school, from which they could graduate, and obtain promotion.
But as in the Army, there are a small number of recruits who languish unassigned, and after a while they are deemed irrelevant, because it is thought that whatever their potential was, it had been wasted through lack of use. It is often thought that it is better for the Army ----and the human body in times when it is in peril of some disease, injury, or in aging---- to bring in altogether new recruits, and to ignore the old ones that were somehow left unassigned.
And such has been the emphasis in stem cell research: Focus on the embryonic ones; underestimate the prospects of the ones that have been in the Army for a long time, but seemingly have not been specially trained or deployed anywhere notably .
WHERE TO FIND WORKING ADULT STEM CELLS? TRY YOUR SKIN & HAIR!
For a long time it was thought that, at least in humans, adults had relatively few stem cells, in a few locations, and they did not seem to do much. They were generally thought of as relicts left over from the active growing processes of ourselves as we developed from embryos to fetuses to infants.
Part of this view resulted from a failure to see that a variety of seemingly specialized “ body repair tissues”, thought of only in the context of their particular organs systems and in therapies related to them, were in fact, actually stem cells.
One of the greatest failures of the public imagination and perhaps of science reporting has been to realize that bone marrow transplants, procedures now done for decades, involve what amounts to stem cells.
But this is scarcely the only example of adult stem cells that has been staring us in the face.
Consider the hair follicle, one of the subjects of an important review in a recent issue of Science (Li and Clevers 2010).
They report that it was not until 2004 that Blainpain et al were able to demonstrate that the hair follicles and surrounding skin not only contained stem cells, but in fact two different types: the quiescent (the kind of seemingly indolent stem cell we expect to find in adults) in the bulge area of the hair follicle, and rather active ones that self-renew their population (in other words, they don’t just sit there, they also provide for their replacement as undifferentiated cells, before they begin the process of turning themselves into whatever specialized replacement cell is needed, in other words, when they enter the TA (Transit Amplifying) stage.
Most of the time, this surprising transformation works remarkably well, but the flip side is evident when this remarkable self-renewal of undifferentiated cells goes awry.
This seems to be the case with the some of the most common (and unfortunately most deadly if untreated) skin cancers melanomas (Cook and Sturm 2008). Their best guess is that beneficial recruitment for skin (and presumably hair) replacement goes bad when a family of cell transcription factors known as POU malfunctions. Not all POU factors are bad, by any means, but the wrong one, or the right one in the wrong place, seems to spell the difference. Marhaba et al (2008) suggest that even adult stem cells that get into a bad neighborhood tend to fall in with a bad crowd: stem cells turn into cancer-initiating cells.
ARE EMBRYONIC CELLS STEM THERAPIES FOR THE HEART LIKELY TO BE THE ONLY WAY TO GO?
There has been significant research on heart attack repair in adult laboratory animals (rats, actually) using human embryonic stem cells (LaFlamme et al 2007), and general discussion of its use on humans (Leor et al 2007) continues. But in a recent review by Passier, van Laake and Mummery (2008), it is pointed out that as far back as 2003 Beltrami et al (2003) demonstrated that while the adult heart is overwhelmingly composed of terminally specialized cells, repair after heart attacks involves a residual population of the body’s own adult stem cells.
The preponderance of stem cell studies in connection with heart attack (and stroke) repair is actually with adult bone marrow lines (see for example, Cesari et al 2010, Edelberg and Ballard, 2008), with mixed, but generally favorable results Gersh et al (2009), but that the injection of reprogrammed adult fibroblasts (cells involved in connective tissue, usually obtained from skin snippets) that are treated to become “plenipotentiary” is probably the most exciting (and least controversial) way to go among many competing approaches.
One possible reason is that while it has not been commonly detected in human trials, a paradoxical outcome seen in animals of bone marrow transplantation to induce heart attack repair may be good heart repair but increased atherosclerosis (Hristov et al 2008).
OTHER ORGANS, OTHER POSSIBILITES
Quite possibly the two other organ system most involved in stem cell based research are those related to diabetes, and to brain and spinal cord repair.
The pancreas contains two types of cells related to glucose regulation and digestion. By far, the greatest interest has been in the beta cells whose absence or poor function is the cause of diabetes. While, based on fundamental studies of the embryonic development of the pancreas, Scharfmann et al (2008) likely represent the majority view that embryonic stem cells hold the greatest promise to enhance the production and performance of these beta cells, Bayens and Bouwens (2008) suggest that pancreatic cells of the other type ----acinar cells----derived from adult cadavers can be reprogrammed into becoming, or at least functioning, like stem cells that will turn into beta cells.
Probably the most overpromised, under-documented, and downright shady practice of stem cell therapy of either embryonic or adult type is done in connection with neurological disorders. Carroll and Borlongan (2008) describe the appalling claims and practices of “stem cell tourist” hotspots that have some bases of operation in the People’s Republic of China, the Carribean, and Eastern Europe. But they also describe their own painstaking progress in the area of using adult stem cells in rodent models, including the surprising finding that a successful experimental therapy that used direct injection into the brain, was actually replicated by using intravenous adult stem cell transplantation.
More work, of course, needs to be done. More work will inevitably be done. But perhaps most intriguingly of all, more of it will involve adult stem cells and their reprogrammed adult cell analogues, than was imagined even a decade ago, when the promise of embryonic stem cells first held our (except for ethical issues) undivided attention.
Tony Stankus, FSLA tstankus@uark.edu Life Sciences Librarian, Science Coordinator & Professor
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Stem Cell Therapy Clinics although experimental is proving to be an incredible tool and one that will be getting alot more press in the months ahead. What is this "hush-hush" procedure? Stem Cell therapy! No - not using someone else's stem cells, YOUR OWN! That's right - and it sounds fascinating.
Posted by: Stem Cell Therapy Clinics | May 10, 2010 at 04:51 AM