Cell Therapy 2.0 – warts and all

Author: David Kent, 03/16/15

The last 15 years of stem cell research have been full of hope and promises – some of it delivered upon, most of it not quite there yet, and some of it miserably failed. I guess that is to be expected in a highly experimental area of medicine, but one of the most striking things for me as a stem cell biologist is the number of times the field has under-estimated the challenges we face. News media typically requires scientists to imagine the simple solution; granting agencies often require the same. Scientists, and businessmen trying to capitalize on scientific discoveries and technologies, feel compelled to play along to continue their funding and this often permeates much deeper than the public relations of media and grantsmanship. The reality, in the vast majority of cell therapies, is that feeding the body a permanent source of cells in the correct numbers and types required to treat individual diseases is an incredibly difficult task.

We are different from each other

One of the most complicated challenges, but simplest in concept, is that people are different from each other. Unlike inbred animal models in which therapies are often first developed, clinical trials must be designed with diversity in mind. Everything from scaling the amount of therapy to understanding the response of an individual’s immune system to foreign cells (or advanced biodegradable devices) needs to be considered – and unfortunately, it turns out our bodies tend to dislike random cell infusions that originate from other people’s immune system. The field of cancer immunology has subsequently exploded and plays a major role in academic sectors trying to understand the whys and hows of this process.

One of the unfortunate consequences of this is that therapies could pass through safety trials (e.g., Phase 1), but would not actually have viable cells doing the proposed job in the patient. This means huge amounts of lost time, lost money, and lost hope – not to mention the distinct possibility that some unscrupulous clinics and companies will exploit the “no harm” therapy and charge very sick people very real amounts of money to have a cell therapy where none of the cells are likely to be alive.

Just because its sexy, doesn’t mean it works

With big challenges come big efforts and some very neat technologies have emerged as a consequence of underwhelming clinical trial results. Scientists and technologists are doing some clever things to try and skirt these problems – and make no mistake, these technologies grab headlines and build excitement.

A good example of this is the attempts to grow insulin producing cells to treat diabetes. Diabetes treatment requires regular production of insulin that can respond to daily intake of food – a massive challenge for cell therapists. One of the sexiest technologies that I have read about is being promoted by ViaCyte – this company is putting progenitor cells in small capsules that can secrete insulin (which is tiny) but are protected from the host immune cells (which are bigger). These capsules are transplanted into a patient and the idea is that the body can support the growth of the cells, but these progenitors would stand apart from immune surveillance – very space aged, very cool. A good technical summary of this approach was recently prepared by Brian Alexander on the MIT Technology Review.

But does it work? Importantly, Alexander’s article is balanced and gets a very candid assessment of the technology from one of the world’s foremost stem cell biologist (Doug Melton). Melton believes that the ViaCyte approach will not deliver sufficient cells and risks being starved of nutrients by the body – two very real potential problems that could make this technology completely useless. The complications involved are many-fold and the list of unknown unknowns could be just as long, but what is very clear is that it is not as simple as replacing a light bulb.

Our bodies are incredibly complicated pieces of biological machinery – we didn’t design them and we don’t have a parts manual, and as a result, I suspect it will take a long time to truly figure out cell therapy. Indeed, I (and many others!) have spent entire careers trying to understand the very basic operations of stem cells in the most well-defined adult stem cell system and even there we are still only scratching the surface of how these cells respond inside a body. There will be exciting pioneering technologies in stem cell medicine and there will be excellent ideas and approaches that will simply fail for unknown reasons. We need to critically assess new technologies, share information across laboratories, companies, and clinics and we need to under-promise and over-deliver rather than doing the exact opposite.

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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 (http://www.stemcells.cam.ac.uk/research/pis/kent). 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.
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