Crystal ball gazing: human embryonic stem cells in 2012

In the last few months of 2011, a couple of stories on human embryonic stem cells (hES cells) hit the headlines. Both were bad news for stem cell researchers.

First, in October, the Court of Justice of the European Union issued its decision in Brüstle v Greenpeace, declaring inventions related to the use of hES cells as not patentable (reported in BioNews 630). The second blow came a month later; the discontinuation of Geron's clinical trial in spinal cord injury (reported in BioNews 634), just under a year after it began, left many in the science community in a state of shock.

And yet this year began with pair of rather more encouraging stories: a clinical trial for dry age-related macular degeneration (a leading cause of blindness and visual impairment) and Stargardt disease (a form of inherited macular degeneration affecting younger people) at University of California Los Angeles (reported in BioNews 642) and the first publicly available fully human clinical grade hES cell lines derived by the team at King's College London (reported in BioNews 637).

There is no doubt that 2012 will bring a similar mixed bag of both disappointing and encouraging news. Which stories will stay in the memory will depend on whether you see a glass of water as half empty or half full. Either way, we should be a step closer to the truth about the power of hES cells.

In today's other BioNews comment article I talk about the implications of the Los Angeles macular degeneration stem cell trial but will add this here: in early clinical trials the priority is always patient safety - in fact that's what the trials set out to establish. Efficacy and economics come later. If anyone expects that the blind patients will regain vision completely after treatment they risk being unnecessarily disappointed. Just remember, because prospects of 'success' were unreasonable from the outset in Geron's trial, a similar safety study, the value of the company's shares dropped by 60 percent in the first nine months of 2011 (the first patient was treated in October 2010).

And other trials are gearing up in macular degeneration. Last year, Advanced Cell Technology received approval for a trial also using hES cell-derived retinal pigment epithelium cells from the Gene Therapy Advisory Committee, the body responsible for ethical oversight of proposals for clinical trials involving gene or stem cell therapies in the UK. The first patient was treated at Moorfields Eye Hospital on 20 January 2012 by a team of surgeons led by Professor James Bainbridge. The same hospital is also a site where, in a collaborative effort with Pfizer, The London Project to Cure Blindness is likely to commence clinical trials for the same disease - age-related macular degeneration - in 2012.

Moving on, there will many more clinical grade hES cell lines surfacing in the UK, not only from King's, but also from other derivation centers at the universities of Manchester, Newcastle, Sheffield as well as at Roslin Cells, a private company. Together with the clinical trials at the Moorfields Eye Hospital, the efforts of researchers at these centres should bring the UK back to the forefront of hES cell-based research, particularly at that all-important 'translational' bridge between lab bench and bedside.

However, we should not forget that in August 2011, the USA National Institutes of Health approved funding for clinical grade hES cell lines, originally made in Singapore from embryos imported from Australia (1). The lines are now distributed through a California Institute of Regenerative Medicine-funded company BioTime for minimal costs to California-based researchers. But it is probably too early for 2012 to see these lines in clinical trials in California. How about Singapore or Australia?

There are other intriguing developments outside the US and the UK. Last year it emerged that the South Korean and Indian authorities are promoting regulated translational stem cell research in their countries. I would not be surprised if stem cell giants such as RNL in South Korea or Reliance Life Sciences and Stempeutics in India, venture to a hES cell-based clinical trial.

All this sounds pretty optimistic and is promising a rosy future for hES cell-based translational research, especially in UK and at least in the near future. Shouldn't we temper this with a healthy dose of cynicism? Yes, we should: we still do not have proof of the concept that hES cell-based therapy can successfully mend damaged tissue and restore rather than just improve its function. Taking the wrong route may hamper cell-based therapy much more than a decision by the Court of Justice of the European Union or discontinuation of a promising clinical trial. What if our approach is wrong and in order to get the best out of hES cells in regenerative medicine, we have to combine cell therapy with gene therapy and biomaterials (encapsulation)? It is about time we think about taking alternative routes.