Published online before print August 19, 2004, doi: 10.1161/01.STR.0000141681.06735.9b
(Stroke. 2004;35:2390.)
© 2004 American Heart Association, Inc.
Original Contributions |
Infusion of Human Umbilical Cord Blood Cells in a Rat Model of Stroke Dose-Dependently Rescues Behavioral Deficits and Reduces Infarct Volume
From the Center of Excellence for Aging & Brain Repair (M.V., J.C., J.N., T.Z., P.R.S., A.E.W.), and the Departments of Neurosurgery (M.V., J.C., J.N., K.R.P., T.Z., P.R.S., A.E.W.), Anatomy (P.R.S., A.E.W.), Pharmacology and Therapeutics (T.B., K.R.P., T.Z., P.R.S., A.E.W.), and Pathology (M.V., P.R.S., A.E.W.), University of South Florida College of Medicine, Tampa, Fla; and Saneron CCEL Therapeutics Inc (C.D.S.), Temple Terrace, Fla.
Correspondence to Dr A. E. Willing, Center of Excellence for Aging & Brain Repair, MDC 78, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd, Tampa, FL 33612. E-mail awilling{at}hsc.usf.edu
Background and Purpose— Intravenously delivered human umbilical cord blood cells (HUCBC) have been previously shown to improve functional recovery of stroked rats. To extend these findings, we examined the behavioral recovery and stroke infarct volume in the presence of increasing doses of HUCBC after permanent middle cerebral artery occlusion (MCAO).
Methods— Rats were subjected to MCAO and allowed to recover for 24 hours before intravenous infusion of 104 up to 3 to 5x107 HUCBC. Behavioral tests (spontaneous activity, step test, elevated body swing test) were performed 1 week before MCAO and at 2 and 4 weeks after HUCBC infusion. On completion of behavioral testing, animals were euthanized and brain infarct volumes quantified. HUCBC were identified by immunofluorescence for human nuclei and by polymerase chain reaction (PCR) using primers specific for human glycerol 3-phosphate dehydrogenase.
Results— At 4 weeks after infusion, there was a significant recovery in behavioral performance when 106 or more HUCBC were delivered (p=0.001 to p=0.05). Infarct volume measurements revealed an inverse relationship between HUCBC dose and damage volume, which reached significance at the higher HUCBC doses (107 cells, p<0.01; 3 to 5x107 cells, p<0.05). Moreover, HUCBC were localized by immunohistochemistry and PCR analysis only in the injured brain hemisphere and spleen.
Conclusions— These results extend previous observations of HUCBC infusion in the MCAO rat stroke model by demonstrating a dose relationship between HUCBC, behavioral improvement, and neuronal sparing.
Key Words: acute stroke • cell transplantation • neuroprotection
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