Published Online
on August 19, 2004

A more recent version of this article appeared on October 1, 2004

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Submitted on April 7, 2004
Revised on May 26, 2004
Accepted on July 6, 2004

Infusion of Human Umbilical Cord Blood Cells in a Rat Model of Stroke Dose-Dependently Rescues Behavioral Deficits and Reduces Infarct Volume

Martina Vendrame MD, PhD; Jordan Cassady BS; Jennifer Newcomb MS; Tanya Butler PhD; Keith R. Pennypacker PhD; Tanja Zigova PhD; Cindy Davis Sanberg PhD; Paul R. Sanberg PhD, DSc; and Alison E. Willing PhD^*

From 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.

^* To whom correspondence should be addressed. 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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