2009: A landmark year for stem cells

It would be fair to say that these past 12 months have been a watershed year for stem cell science. In years to come we may look back on 2009 and recognise it as the year in which nascent areas of science, medicine and technology came together to slowly nudge stem cell biology into the mainstream. Scientific and academic progress aside, it also may mark the year in which the field first matured to a stage at which commercial viability came to the cusp of realisation.

Developments in the field that reflect this assessment can be cast in the broad categories of the regulatory and legislative environment, the focus of large players on therapeutic potential and regenerative medicine, and the industrialisation and commercialisation of cells for drug discovery and toxicological applications.

The regulatory environment, and ensuing media hype, around progress in stem cell biology has always been, and will likely for some considerable time continue to be, a contentious issue for many. From the perspective of a research scientist, whether in industry or academia, President Barack Obama’s lifting of restrictions on US federal funding for research on human embryonic stem cells in March, was a huge and welcome step forward. It signaled the opportunity for billions of dollars of federal funding for stem cell research, and while there is still a long way to go from a regulatory perspective, never mind the science, this move counts as very real progress along the road to getting potential therapies through research and into practice where they can begin to benefit patients.

Couple this with the FDA granting Geron clearance for the first in-human clinical trial of an embryonic stem cell-based therapy (for the treatment of complete thoracic spinal cord injury), and you have two highlights of progress in a field that is not really much more than 15 years old.

If you consider Geron’s achievement in the context of run-of-the-mill drug discovery, if there still exists such a thing, the acceleration in the process is remarkable. To take a new and yet-to-be fully understood potential therapeutic from early research, through to developing a protocol robust enough to satisfy the FDA that it is ready for the clinic in just 10 years, represents an outstanding series of achievements, both scientific and regulatory, in a field that is arguably still in its infancy.

At the time of writing, Geron’s trial is still under clinical hold by the FDA, and some might flag this as a setback for the field as a whole. This however, has to be seen in the context outlined above. The FDA is right to progress cautiously in such a new and untested area; the decisions it makes now will have repercussions on the field as a whole for years to come. Geron says it has reached an agreement with the FDA on what would be required to allow the programme of early stage trials to restart, and hopes to do so by the end of 2010.

If Geron is successful and this therapy is proven both safe and effective, it will be a tremendous boost to the industry as a whole, and potentially serve to alleviate many of the anxieties surrounding the use of stem cells in general and human embryonic stem cells in particular. With a first successful hESC-based therapy on the market, we should see mainstream acceptance of the therapeutic field gain further momentum.

The interest that major pharmaceutical companies are showing in stem cell technology and regenerative medicine is the second development that marks the past year as a milestone in the field. While the practical applications may yet remain ill-defined, there is clearly a growing acceptance that the potential commercial application of stem cell science has moved from the long-term future to being firmly on the horizon.

In 2007, R&D China (GSK) became the first large pharmaceutical company to announce the introduction of human stem cells in their drug discovery processes and the establishment of a $25 million research collaboration between GSK and the Harvard Stem Cell Institute heralded a new type of industry-led research effort. Similarly in 2007, Pfizer established two Centres for Regenerative Medicine, based in Cambridge, Massachusetts and Cambridge, UK, to develop therapies for heart disease and diabetes, and retinal and nervous system disease, respectively. Although there have not been any similar major big pharma-led initiatives this year, there is a sense of a growing interest and acceptance by the pharmaceutical industry of the potential utility of human stem cells in the drug discovery and development of novel therapies.

Thirdly, advances in the potential for the commercial use of stem cells for predictive toxicology in drug discovery, highlight the fact that there is increasing acceptance of a trend that was highlighted perhaps first in 2007 with the creation in the UK of Stem Cells for Safer Medicine (SC4SM) with the long-term objective of developing a bank of differentiated human cell lines to be used in early drug discovery to provide early identification and elimination of potential toxicity issues before clinical testing.

This area has come a long way since 2007, with researchers at University of Edinburgh’s MRC Centre for Regenerative Medicine and Harvard Medical School reporting in October this year that they had used induced pluripotent stem cells (iPSC) to create hepatocytes that could be used in toxicology testing to replace today’s gold standard primary human hepatocytes which are in short supply as they come from donors or dead tissue. GE Healthcare has elected to partner with Geron in this field, and has gone down the route of working together using hESCs to develop commercial cellular assay products for use in in-vitro assay applications, including drug discovery and development and toxicology. It is too early too tell whether it is hESC or iPSC technology that will prove the more useful, flexible and commercially viable in this field, and I suspect it may be a combination of the two, but either way, the entrance of a major multinational player such as GE Healthcare into the field is a sure-fire sign that commercial viability is not just around the corner, but is staring us in the face.

Challenges remain, however. Cell proliferation and differentiation is a challenge across both the therapeutic and drug discovery applications. Considering the numbers of cells that will need to be generated for predictive toxicology, and the consistently high standards of quality and predictability at which they will need to be produced, the demands are tremendous. Protocols and procedures need to be developed that will enable such cells to be produced in an “industrialised” fashion, on a daily basis to GMP standards.

The same applies for clinical and therapeutic use, and as yet the question remains unanswered: just how will the trillions of cells required for routine therapeutic applications be generated under GMP conditions required for human clinical use? Who will generate the cells? Big pharma and biotech, or will we see the implementation of national stem cell processing centre’s similar to the National Blood Service? Who and how will this be funded? Will treatment be predominantly allogenic with the associated immunological issues or can autologous cell therapy for thousands of individuals a year ever be realistic?

There are a number of important technological and biological hurdles that currently impede the quick translation of human stem cells as therapeutic agents and validated research tools, but given the rapid and progressive march of research in this field, it will only be a matter of time and effort before the full potential of these amazing cells are realised.