Jan 20 2009

Stem Cells for Stroke

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Dr. Keith Muir is leading a trial at the Southern General Hospital in Glasgow that is about to test stem cells as a possible therapy in stroke. As reported by the BBC, the trial is set to enroll 12 subjects and will last for two years. While this will be far from a definitive trial, it will explore the basic safety and potential of this approach.

Strokes occur due to lack of blood flow to a part of the brain. Those brain cells are injured – those at the core of the stroke die while those around the periphery (which is usually much larger in volume than the core), which are getting some blood flow, may or may not survive. About a third of stroke patients recover either fully or nearly so, while the rest either die or suffer permanent neurological deficits. The symptoms of a stroke depend upon what part of the brain is damaged.

Dead brain cells do not come back. Initial recovery results from damaged but not dead neurons recovering their function. After that, deficits are due to dead brain cells and are considered permanent. However, further recovery is possible (although slow – months to years) due to the brain’s plasticity. The brain can rewire around damaged section, and form new pathways. In addition, healthy cortex can take over the lost functions or compensate for them to some degree. This takes a great deal of time and effort, which is part of the function of the long course of rehabilitation that often takes place following a stroke.

In recent years it has also been discovered that there are neuronal stem cells even in the adult brain. These cells are activated whenever part of the brain takes on a new task that requires new pathways. This may be why undertaking novel mental tasks later in life may stave off degenerative brain diseases.

But the brain’s plasticity has its limits. When large parts of the brain are damaged by stroke the lost functions can only be partially compensated for. Further, after such a recovery the brain has lost some of its reserve. It is not uncommon, for example, for the symptoms of a stroke that one has recovered from to return under stress – sleep deprivation, emotional stress, or a mild fever.

Stem cell therapy holds the promise of implanting additional neuronal stem cells into a patient’s brain following a stroke, and then these stem cells contributing to recovery. In effect they would dramatically increase the plasticity of the brain, the new cells being recruited to form new pathways to take over for lost function. Because the brain already is a plastic organ – it can direct the neurons to form new and meaningful connections – this is a very plausible scenario.

But of course plausibility is not enough. There are many hurdles to such a technology. We need to get stem cells to become neuronal stem cells, to survive after transplantation, and to become recruiting into repairing the brain. Further, we need to make sure that these introduced cells do not just grown into a tumor. That is the reason for the caution, and why clinical trials of stem cells in humans have been so slow.

Also slowing the process are the controversial moral concerns. Such studies have not taken place in the US because the FDA has not approved any such trials. Further, George Bush’s ban on making new stem cell lines and the limitations on federal funding have greatly impeded stem cell research here. Other countries have tried to take advantage of this opening and take the lead in this new technology. Korea was thought to be in the lead for a while, but then the fraud scandal greatly set them back. Now the UK is hoping to take the lead. Although Obama is likely to almost immediately get rid of the Bush Administrations constraints on stem cells, the controversy will not go away and it will take years for American research to recover.

Meanwhile, opposition to stem cell research among the religious right remains strong. In response to this current study, a spokesperson for Society for the Unborn Child is quoted as saying:

“It involves cannibalising an unborn child.  It is unethical in every way – killing one member of the human race to help another. We are totally opposed to this.”

Extreme rhetoric such as this does not foster much hope for a reasonable dialogue.

Then again, there is research that is progressing very nicely into the technology to transform an adult derived cell into a stem cell – so-called induced pluripotent stem cells. A team in Japan discovered that changing only four genes is all that is needed to induce pluripotency. Recently a team in Boston was able to duplicate these effects with a single viral vector – one virus to implant all four genes.  If this technique pans out it could end the controversy surrounding embryonic stem cells completely.

There are a lot of “ifs,” but that’s why it’s research. Twenty or thirty years from now people might be wondering “what ever happened to stem cells, remember them?” Or they might wonder “what did people do before stem cell therapies?” as if such a primitive existence is beyond their imagination. I certainly hope it’s the latter, and I think it’s worth the research dollars to find out.

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