Stem Cells to Rescue Stroke Patients

[box] Utsav Radia explains the science behind promising future stroke treatment [/box]

Every year, there are approximately 152,000 strokes in the UK, costing the economy a whopping £7 billion. Last year, 19,710 people were admitted to hospital following a stroke in the UK. It is predicted that 20% of strokes are fatal – those that survive fall prey to the aftermath of disability and distress. Currently in England, more than 900,000 people are living with the effects of stroke, with 50% dependent on someone else for assistance with even the simplest day-to-day activities such as getting dressed and eating.

Fortunately, a recent breakthrough by researchers at Imperial College London, led by Dr Soma Banerjee of Imperial College London NHS Trust, may provide a means to revolutionise the way we treat stroke. Dr Paul Bentley, from the Department of Medicine at Imperial College and co-lead author of the study, said it is “the first trial to isolate stem cells from human bone marrow and inject them directly into the damaged brain area using keyhole techniques”. The study, published in the journal Stem Cells Translational Medicine, used haematopoietic stem cell precursors to stimulate angiogenesis and improve functional recovery in patients with ischaemic stroke.

A stroke, or cerebrovascular accident (CVA), is defined as: ‘the interruption of blood flow to the brain or the brainstem resulting in impaired neurological function lasting more than 24 hours’; whereas, if the neurological impairment resolved within 24 hours, it is called a transient ischaemic attack (TIA). Broadly speaking, there are two main types of stroke: ischaemic and haemorrhagic. Ischaemic strokes are those that are caused by emboli (generally blood clots) that migrate into and block smaller intracranial blood vessels; they are accountable for up to 85% of strokes. On the other hand, haemorrhagic strokes are caused by rupture of a weakened blood vessel wall. Common risk factors include hypertension, diabetes, smok- ing and male gender – similar to cardiovascular disease. Although the incidence is greater in over 65s, underlying clotting disorders, use of oral contraceptives and illicit drug use are common causes of strokes in younger adults and children.

Evidently, it is crucial that a stroke is diagnosed accurately so that effective and potentially life-saving treatment is administered in time. Validated tools such as FAST (Face Arm Speech Time) are suggested to screen for stroke and TIAs in out-of-hospital environments. Despite the recent questions raised on its safety, under NICE guidelines, alteplase (a recombinant tissue plasminogen activator) is recommended for treating acute ischaemic stroke, albeit by trained and experienced physicians. However, in order to be functionally effective, it must be administered within 3-4.5 hours of the thrombotic episode and is contraindicated in haemorrhagic stroke, where it can exacerbate the bleeding. Haemorrhagic stroke is diagnosed mainly by a CT scan. These stringent regulations mean that unless specialised imaging and rapid response facilities are at hand, the use of fibrinolytic agents is limited. Previously, it was suggested that neuroprotective agents (such as glutamate antagonists, calcium and sodium channel blockers and NMDA receptor antagonists etc.) aimed at limiting the damage done on the outer edges of the lesion would be useful clinically. Unfortunately, these drugs were reported to fail at the clinical trial stage in animal models and so the concept wasn’t taken any further.

Stem cell therapy has been an emerging new therapeutic concept and is based on the premise that certain parts of the human brain are capable of regenerating. The ‘endogenous’ approach involves stimulating haematopoietic precursors in the individual to release chemical factors such as Granulocyte-Colony Stimulating Factor (G-CSF) that aid with brain tissue regeneration and angiogenesis. The ‘exogenous’ approach involves transplantation of stem cells, delivered locally or systemically to the individual for more direct effects. However, as with other uses of stem cells, there have been many ethical and legal questions raised regarding the origin and safe harvesting of therapeutically used stem cells.

The new research done by scientists at Imperial College London involved harvesting bone marrow from each of the five patients sampled and sending it to a specialist laboratory where specific CD34+ cells could be isolated. These cells were then subsequently delivered via catheter angiography (a process that involves inserting a wire through an artery that supplies the brain) into the brain using the ipsilesional middle cerebral artery as a bypass. The idea behind this was that the CD34+ would stimulate angiogenesis (the growth of new, healthy blood vessels) which would facilitate the growth of new nerves and healthy brain tissue as well as release anti-inflammatory mediators that stimulate tissue regeneration.

In this study, patients were treated within seven days of the stroke, as opposed to other trials that involve treatment after 6 months or later. Patient outcomes were measured using the Modified Rankin Scale (MRS) and NIHSS score over a 6 month follow-up period; all patients showed improved clinical function.

Understandably, the clinicians involved in the trial agreed early intervention for stroke patients holds the key to successful clinical outcomes. Dr Soma Banerjee, lead author of the study, said “the treatment appears to be safe and the improvements we saw in these patients are very encouraging” but was modest in mentioning that “it’s too early to draw definitive conclusions, we need to do more tests and work out the best dose and timescale for treatment before starting larger trials”. Also thrilled with the findings was Professor Nagy Habib, from the Department of Surgery and Cancer at Imperial College, who said the data is “exciting” and explained “evidence from our lab further supports clinical findings. Our aim [now] is to develop a drug, based on factors secreted by stem cells, that could be stored in the hospital pharmacy”. Although, it seems as though the research is in its initial stages of development, it seems we are not far off from being able to provide another means of immediate and long-term treatment for stroke patients.

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