Signals Blog

A CCRM scientist pipetting cells

Over the Christmas break, I finally got around to reading an article that has been in my “to read” pile for far too long. For anybody new to the regenerative medicine and cellular therapy fields, it is an absolutely fantastic resource to catch up on some of the biggest issues. “Lancet Commission: Stem cells and regenerative medicine,” by Giulio Cossu and colleagues, details the inner workings of the cellular therapy and regenerative medicine fields with a keen eye on establishing robust frameworks for moving forward with promising therapies and treatments.

There is a lot to digest in the article and far too much to talk about in a single blog entry, so I thought I would focus on one of the most pressing problems for the field, in my opinion. About halfway through the article, on page 11, there is a short section entitled “Small trials, difficult statistics, difficult regulation, and data reproducibility,” and I think this is perhaps one of the most underestimated problems of the cellular (and gene) therapy fields.

The article first points out that for some therapies – in particular gene therapy of single hit disorders – the black and white outcome of “alive” versus “dead” is quite easy to measure and therefore easy to regulate. However, the vast majority of therapies would fall somewhere in between. What are we to do about those? Cellular therapies are particularly difficult because they are often designed on a patient-by-patient basis, and the “product” is a one-off batch of cells that goes into a single patient, making most cell therapies incredibly expensive.

This, in turn, causes several problems:

  • Small trials – it is difficult to afford hundreds (let alone thousands) of patients;
  • Non-random patient selection – if there are only 10 or 20 patients in a cellular therapy trial, there is an enormous pressure to get patients for whom the therapy will work; and,
  • Lack of randomized control groups – few people would want to be a placebo control in a cellular therapy that costs hundreds of thousands of dollars.

When writing last year about baseball pitchers receiving stem cell therapy, I commented that “Since this is such a niche injury and the stakes are so high (professional athletes are big $$$), you can virtually guarantee that nobody will ever undertake a sham injection or volunteer to be the untreated control” and this is, to an extent at least, the same problem with the cellular therapy industry as a whole…  how DO you fairly evaluate highly experimental and expensive therapies?

The result? Many evaluations feel forced and are of a very poor standard (not enough patients, poor regulation, absence of reproducibility and few multi-centre validations). So where does this leave the field? For the answer, I return to the Cossu article for a number of excellent suggestions (paraphrased) that should be taken very seriously as the field moves forward:

  • Preclinical work (animal models, cell lines, etc.) should be held to the same rigorous standards as the clinical trial itself.
  • An international register of cell and biological experimental interventions (i.e., cell therapies) should be created and no trial should be permitted without entry into this registry.
  • The initial review for every experimental therapy should consider the relevant social and regulatory context.
  • Researchers and others involved in funding, publishing and communicating stem cell research should integrate some responsibility for public dialogue into their research.

The scientist in me would argue that the second point is the most critical. We need to track cellular therapies that are already being performed, and record and analyze the successes and failures in an unbiased and comprehensive fashion.

But perhaps more important to the reader is the need to push the field to increase efforts that would prevent rogue clinics from cashing in on completely unrelated successful therapies (e.g. the hype that is brought about by a sensational set of recoveries). Improving the standard of preclinical research, registering all therapies and assessing the societal context of the therapy will all help to ensure that potential cellular therapies are evaluated properly and lead to better overall management of an exciting, but sometimes deeply troubling, emerging field of medicine.

(N.B., for those curious about the lack of attention paid to point #4, I’m working on another article related to the responsibility of scientists to think beyond their own research experiments.)



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David Kent

David Kent

Principal Investigator at University of Cambridge
Dr. David Kent is a Principal Investigator at the University of Cambridge in the Cambridge Stem Cell Institute ( His laboratory's research focuses on fate choice in single blood stem cells and how changes in their regulation lead to cancers. David is currently the Stem Cell Institute’s Public Engagement Champion and has a long history of public engagement and outreach including the creation of The Black Hole in 2009. He has been writing for Signals since 2010.