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).
OBJECTIVE
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 microg/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 microg/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.
Sprigg
Nikola
N
Institute of Neuroscience, University of Nottingham, Nottingham, UK.
Bath
Philip M
PM
Zhao
Lian
L
Willmot
Mark R
MR
Gray
Laura J
LJ
Walker
Marion F
MF
Dennis
Martin S
MS
Russell
Nigel
N
D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods; D002545:Brain Ischemia / Q000188:drug therapy / Q000453:epidemiology / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D011994:Recombinant Proteins; D020521:Stroke / Q000188:drug therapy / Q000453:epidemiology / Q000601:surgery*
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor