Genetics and stem cells

'Safe' stem cell therapy may help stroke recovery

BBC Online today reports that "Stem cells show promise in stroke recovery".

This accurate headline comes from a study showing how a new technique using a patient's own stem cells to aid recovery from severe ischaemic stoke is feasible and appears to be safe.

But the study was tiny – just five people had the treatment. The study was also not designed to test whether the technique was effective, only whether it was feasible and safe.

This means we cannot be sure the improvements seen in the patients were caused by the stem cell treatment itself. They could have occurred anyway as a natural path of recovery post-stroke – a point the study authors explained.

A much larger trial that compares this stem cell treatment with the best available care would be needed to prove effectiveness, and is a logical future step for this treatment in development.

The well-worn path of treatment development is often long and costly, but is designed to protect patients from potentially harmful treatments, and weeds out all the treatments that are not effective.

However, we should not ignore the fact the technique was well tolerated in the five people and did not appear to lead to any side effects in the six months it was evaluated – a promising result.

Where did the story come from?

The study was carried out by researchers from Imperial College Healthcare NHS Trust and Imperial College London.

It was funded by Omnicyte Ltd – a British-based biotechnology company specialising in extracting the therapeutic potential and benefits of stem cell technologies.

The study was published in the peer-reviewed science journal, Stem Cells Translational Medicine.

Generally, the media reported the story accurately, with the BBC explaining that the treatment was in its very early stages and that this latest study was designed to test the safety and feasibility of the stem cell treatment, rather than its effectiveness.

What kind of research was this?

This was a proof-of-concept, non-randomised, open-label, human trial. It looked at whether a new stem cell infusion technique in development was feasible and safe to treat patients with acute severe stoke within seven days of it occurring.

The study focused on people who'd had an ischaemic stroke – when blood supply to the brain is cut off either because of a narrowing of the vessels supplying the brain, or because there is a blood clot in these vessels. Most strokes happen suddenly, develop quickly and damage the brain within minutes.

The study was a small feasibility study, meaning it was not designed to provide solid proof that the treatment worked. Instead, its main aim was to see if the technique was possible to use and was safe in a small number of people.

What did the research involve?

The researchers wanted to recruit people who could start treatment within seven days of stroke onset and if they had a stroke with particularly severe characteristics.

According to Imperial College, this "total anterior circulation stroke" (TACS) usually has a poor outcome in most people. Typically, just 4% of people who have a TACS stroke are alive and living independently six months after the stroke. For this reason, any treatments that can improve outcomes are extremely welcome.

The researchers excluded people if they were over 80, "medically unstable", had a significant narrowing of the carotid artery, or declined or were unable to participate. However, the researchers had trouble recruiting enough people with this subtype, so the inclusion criteria were widened to include the partial anterior circulation stroke (PACS) subtype of ischaemic stroke.

In the end, five patients who had experienced a clinically confirmed severe stroke in the past seven days (four had TACS stroke, one had PACS stroke) were recruited (out of 82 screened). Each had a small amount of bone marrow extracted under local anaesthetic.

This bone marrow was purified to isolate the patient's own CD34+ stem cells, which were injected into the patient's arteries one or two days later. Side effects were documented for six months after treatment.

The researchers also recorded the degree to which the stroke impaired normal daily functioning using validated clinical rating scales (National Institutes of Health Stroke Scale and modified Rankin Scale), and how well their brains recovered by looking at MRI scans.   

The researchers said they used CD34+ stem cells because they had improved functional recovery in non-human models of ischaemic stroke by promoting blood vessel and nerve cell growth.

The study was designed primarily to test safety and was not designed to prove whether the treatment significantly improves the lives of the participants with any rigour. Much larger trials involving treatment randomisation and control groups would be required for this.

What were the basic results?

The main results were:

  • All five patients reportedly tolerated the procedure well with no complications. There were no recurrent strokes and no nerve deterioration during the six-month follow-up period.
  • All patients showed improvements in the clinical ratings of how their stroke impaired their day-to-day functioning from the start of the trial and six months later.
  • The size of the areas of damage assessed by MRI scan reduced in all patients over the six months by 10% to 60%. The average change was 28% at six months' follow-up.
  • There were no signs of tumour growth or blood vessel malformation, which is a potential side effect of injecting stem cells.

How did the researchers interpret the results?

The researchers state they "have demonstrated in a phase I clinical trial that autologous CD34+ stem/progenitor cells [stem cells originating from a patient's own body], delivered directly into the middle cerebral artery within the first week of stroke symptoms, is both possible and safe."

They noted: "All patients showed improvements in clinical scores and reductions in lesion volume within six months. Although such patterns of recovery are well recognised in the usual natural history of strokes, these findings are nevertheless reassuring for future trials of CD34+ cell therapy. In particular, we found no evidence of post-intervention stroke (ischaemic or haemorrhagic), vascular malformation or tumour."


This study provides evidence that a new technique using a patient's own stem cells to aid the recovery from severe ischaemic stoke is feasible and appears to be safe. It was not designed to test whether the technique was better than doing nothing or better than other types of care or treatment.

The authors are perfectly clear that this "proof-of-concept study was not designed with a control group or powered to be able to detect efficacy". This means we cannot be sure that the improvements seen in the five patients were caused by the stem cell treatment. They could have occurred anyway as part of the natural path of recovery after a stroke – a point made by the authors.

A much larger trial that compares this stem cell treatment with the best available current care is needed to prove its effectiveness.

It may surprise some people to learn that a trial of a new treatment did not actually set out to test whether the treatment worked. This is normal in the sequence of treatment development.

When researchers find a new potential treatment, usually through animal research, they then need to demonstrate that the treatment is feasible to carry out in humans and, most importantly, that it is safe.

To do this, they typically recruit a small number of people and monitor them intensely – as happened in this study. If the treatment is deemed feasible and safe in this small group, they can design larger trials, which aim to both optimise the treatment and prove that it works.

This well-worn path of treatment development is often long and costly, but is designed to protect patients from potentially harmful treatments and weeds out ineffective treatments.

In a press release, the research team say they aim to develop a drug based on this technology, rather than performing the time-consuming bone marrow extraction, purification and injection steps.

They hope that giving the treatment quickly, and in drug form, is more likely to improve patients' chances of recovery than slower alternatives. To do this, they hope to isolate the biological factors secreted by the stem cells and harness these into a drug.

This could be stored in a hospital to be given quickly to a person admitted to A&E after a diagnosis of stroke. This could potentially shorten the treatment time from days to hours.

However, we should not ignore the fact this latest technique was well tolerated and did not appear to lead to any side effects in the six months it was evaluated – a promising result for the patients and researchers involved. The next test will be to see if it works, and how it compares to other treatments and standard care.

NHS Attribution