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(Stroke. 2006;37:2979.)
© 2006 American Heart Association, Inc.

Original Contributions

Granulocyte-Colony–Stimulating Factor Mobilizes Bone Marrow Stem Cells in Patients With Subacute Ischemic Stroke

The Stem Cell Trial of Recovery EnhanceMent After Stroke (STEMS) Pilot Randomized, Controlled Trial (ISRCTN 16784092)

Nikola Sprigg, MRCP; Philip M. Bath, MD; Lian Zhao, PhD; Mark R. Willmot, MRCP; Laura J. Gray, MSc; Marion F. Walker, PhD; Martin S. Dennis, MD Nigel Russell, MD

From the Institute of Neuroscience (N.S., P.M.B., L.Z., M.R.W., L.J.G., M.F.W.) and Department of Haematology (N.R.), University of Nottingham, Nottingham, England, and the Department of Clinical Neuroscience (M.S.D.) University of Edinburgh, Edinburgh, Scotland.

Correspondence to Prof Philip Bath, Stroke Trials Unit, University of Nottingham, D Floor, South Block, Queen’s Medical Centre, Nottingham NG7 2UH UK. E-mail philip.bath{at}nottingham.ac.uk

Background and Purpose— Loss of motor function is common after stroke and leads to significant chronic disability. Stem cells are capable of self-renewal and of differentiating into multiple cell types, including neurones, glia, and vascular cells. We assessed the safety of granulocyte-colony–stimulating factor (G-CSF) after stroke and its effect on circulating CD34+ stem cells.

Methods— We performed a 2-center, dose-escalation, double-blind, randomized, placebo-controlled pilot trial (ISRCTN 16784092) of G-CSF (6 blocks of 1 to 10 µg/kg SC, 1 or 5 daily doses) in 36 patients with recent ischemic stroke. Circulating CD34+ stem cells were measured by flow cytometry; blood counts and measures of safety and functional outcome were also monitored. All measures were made blinded to treatment.

Results— Thirty-six patients, whose mean±SD age was 76±8 years and of whom 50% were male, were recruited. G-CSF (5 days of 10 µg/kg) increased CD34+ count in a dose-dependent manner, from 2.5 to 37.7 at day 5 (area under curve, P=0.005). A dose-dependent rise in white cell count (P<0.001) was also seen. There was no difference between treatment groups in the number of patients with serious adverse events: G-CSF, 7/24 (29%) versus placebo 3/12 (25%), or in their dependence (modified Rankin Scale, median 4, interquartile range, 3 to 5) at 90 days.

Conclusions— G-CSF is effective at mobilizing bone marrow CD34+ stem cells in patients with recent ischemic stroke. Administration is feasible and appears to be safe and well tolerated. The fate of mobilized cells and their effect on functional outcome remain to be determined.

Key Words: ischemic stroke • stem cells • colony-stimulating factors • stroke recovery

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