Stem cell therapies - balancing risks and benefits

By Louise Cameron

5 July 2016


Regenerative medicine, a field that encompasses stem cell therapy, has been described by George Osborne as one of the UK’s ‘eight great technologies’. The level of excitement, justified or not, surrounding the stem cell science and its therapeutic benefits is enormous. Consequently, funding for research and development in this field, both in the UK and abroad, continues to be a major priority for governments and industry. It’s easy to see the allure of therapeutic strategies that can promise a potentially limitless supply of cells without issues of rejection, or living drugs which can replace a raft of potentially toxic pharmaceuticals. Enthusiastic reporting in the press might lead us to think we are just around the corner from a paradigm shift towards cellular therapeutics for diseases as diverse as Alzheimer’s, diabetes and cancer, but what’s really going on in the research laboratories, and hospital clinics?

What are stem therapies? - view our updated explanation here

What are stem cell therapies and what can they do?

There are four distinct sources of stem cells which may be used in stem cell therapies: embryonic stem cells, cord blood stem cells, induced pluripotent stem cells, and adult stem cells. In our appraisal of the technology, we’ve focused on the latter. 

Stem cell therapies make use of relatively unspecialised cells which can be converted (inside or outside the body) to more specialised cell types that can repair or restore function to diseased or damaged tissue or to provide therapeutic functions. For example, researchers are examining the use of stem cells to repair damaged heart tissue following a heart attack. 

Stem cell transplants are well-established for use in treating blood cancers, where bone marrow stem cell transplants have been in use, to great effect, since the 1970s. Technological advances are paving the way for the growth of a greater variety of tissues and organs for transplant using a wide array of adult stem cells.  The use of adult stem cells has some advantages, so the discovery that they could be used in a number of different therapeutic contexts was important, not least because such an approach avoids the ethical, regulatory and technical challenges associated with embryonic stem cell use. One example of this wider application of stem cells is the growth of laryngeal implants for transplant in patients with stenosis of the upper windpipe or voicebox, using an anatomical scaffold seeded with cartilage and mucous-membrane cells derived from the patient’s own bone marrow stem cells.

Stem cells can also be combined with advanced genome editing techniques, potentially heralding a new era in cancer treatment – to the extent that they have been described as the ‘fifth pillar’ of cancer treatment. Genome editing can be used, in an advanced form of immunotherapy, to add in genes, giving the immune cells the ability to recognise specific cell markers on the malignant cells and destroy them. This includes some types of Chimeric Antigen Receptor (CAR) T-cell therapy, similar to the treatment received at Great Ormond Street Hospital by Layla Richards.

So why aren’t more people being offered a stem cell therapy now?

Currently, the only clinically approved uses of stem cell therapy in the UK are limited to bone marrow stem cell transplants for leukaemias and lymphomas, skin cells for repairing skin in the case of burns, and corneal stem cells for some forms of ophthalmic disorders. Subject to regulatory approval, experimental stem cell therapies can sometimes be offered as ‘one-off’ specials on a named patient basis.

The current situation reflects two key challenges that remain to be addressed by the panoply of organisations involved in the development and regulation of these therapies including the Medicines and Healthcare products Regulatory Agency (MHRA), the Human Tissue Authority (HTA), Human Fertilisation and Embryology Authority (HFEA), the Genetic Therapy Advisory Committee (GTAC) and the Health Research Authority (HRA) in the UK. 

(i) Technical complexity- identifying and purifying the correct cells, under tightly controlled laboratory conditions means the workup prior to any clinical trial is a technically challenging endeavour. Most UK trials are currently in Phase I or Phase II with a few Phase III trials and therefore the evidence base for clinical effectiveness is relatively undeveloped at present.

(ii) Secondly, legitimate concerns about safety and our stringent regulatory system means that an imminent expansion of clinically approved stem cell therapies is hard to envisage. All medicinal products are put through their paces before they can be administered, and the potential lifelong exposure of ‘living drugs’, difficulties in establishing dosage and unknown long term effects in terms of ectopic tissue formation or tumour growth, mean that stem cell therapies have an even greater number of  regulatory challenges to satisfy.

Responsible innovation - getting the balance right

The bespoke nature of many stem cell treatments and the small numbers of patients who would be eligible for clinical trials adds to the challenge of building a satisfactory evidence base demonstrating both safety and effectiveness of these approaches. The ‘gold standard’ RCT data which is required to establish safety and clinical utility is very hard to accumulate for such treatments, where patient numbers are small, and in some cases the therapies must be individually produced. This challenge isn’t new. A glance back through medical history teaches us that what was once considered risky can sometimes go on to become well-established in medical care - think heart transplants and IVF. We must not forget that many transformative medical innovations have required pioneering patients and clinicians to take substantial risks, which we as a society now benefit from.

Our expectations as patients, clinicians, funders and commissioners are continually evolving so that our assessment of risk must be transparent, reasoned and defensible. We demand innovative solutions to our healthcare problems, but expect that our treatment will not have any harmful effects - not always the easiest balance to strike. A number of initiatives are currently trying to improve access to novel treatments in such a balanced way, for example the Accelerated Access Review and the Early Access to Medicines scheme.

So while the potential for therapeutic stem cell technologies is undoubtedly worth getting excited about, and the regulatory and funding climate is looking more favourable than in the past, we must be patient as the evidence base grows and be realistic about the timeframe within which we will see more widespread benefits.

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