Tuesday, April 21, 2009

ESCs, iPS or ASCs for macular degeneration: a no-brainer.

Yes, you read it in The Australian, that "an (embryonic) stem cell therapy to cure the most common cause of blindness has been developed. Surgeons predict it will become a routine one-hour procedure that will be generally available within seven years."


To the experienced eye, this is clearly another calculated bubble of hype – but for sake of argument, let's pretend this speculation actually might come to pass 'within seven years'. Then, in order to gently deflate this – or any – ESC bubble, let us ask the two key questions that any reasonable person must always ask:


  1. Why use embryonic stem cells (ESC) when you can use induced pluripotent stem cells (iPS)? We know the two types are indentical in their properties, but there is one huge clinical difference: iPS cells match the patient, and ESCs do not. ESCs are foreign cells from a foreign individual, and require immune suppressants even in animal studies, to prevent rejection – just like with an organ transplant. Which would you, the patient, prefer?
  2. For that matter, why use either ESC or iPS when you can use adult stem cells (ASC)? We already have reports of the capacity of ASCs to generate the same retinal cells generated by ESCs in this 'breaking news'. Again, there is not one but TWO huge clinical differences. ASCs, like iPS cells, match the patient – but ESCs are foreign. Further, ASCs alone are free from the tumour risk inherent in ESC / iPS cells. Which type of cell would you, the patient, prefer to have in the back of your eye?

In one example of ASCs used to generate retinal photorececeptor cells – published in the journal Stem Cells last year – the principal researcher comments on both the immune-rejection and ethical advantages:

Dr. Ahmad's research team recently published its findings in the journal Stem Cells. Their findings demonstrated that corneal stem cells could be converted into photoreceptors, he said, which suggests that they also could be used for repairing retinal damage. "This gives us hope that we may be able to manipulate these cells to treat retinal degeneration and restore sight," he said. "By using a person's own Muller adult stem cells, problems associated with immune rejection as well as the controversy surrounding the use of embryonic stem cells would be eliminated."


No, even if reckless authorities in the UK were to approve this proposed ESC trial, and risk tumours and immune rejection in the delicate ocular tissues of volunteers, sensible 'customer demand' will have the final say. No reasonable person will prefer ESCs – with all their ethical ugliness and need for innume suppressant drugs – over the simple and clean technique of iPS. Further, this reasonable person would not let either ESCs or iPS cells within a metre of my retina, when I could use ASCs instead and have no concern over tumours.


And finally, only ASCs are on track to treat the other aspect of macular degeneration – abnormal blood vessels in the retina.


For example, see Nature journal in 2002 – reviewed here. The researchers comment:

"Abnormal angiogenesis is the cause of visual loss in age-related macular degeneration, where new blood vessels grow under the retina.In the ocular disease models, the (adult) stem cells differentiated into endothelial cells and proliferated, forming new blood vessels. This actually rescued and stabilized the retinal vessels when they would otherwise be degenerated."


Or peruse the full article in the Journal of Clinical Investigation, 2004:

"In this study we demonstrate that whenever a fraction of mouse or human adult bone marrow–derived stem cells rescues retinal blood vessels that would ordinarily completely degenerate, a dramatic neurotrophic rescue effect is also observed."


Memo: whenever a claim for ESC therapy is made, always ask the two question: Why not use iPS and get a perfect genetic match? Why not use ASC and avoid the tumour question?


Never forgetting the one question that overarches this whole debate: Why not get this good science in an ethically uncontentious way, using a method that dose not exploit human embryos?