Background and Purpose-Intravenously delivered human umbilical cord blood cells (HUCBC) have been previouslyshown 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 10 4 up to 3 to 5ϫ10 7 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 10 6 or more HUCBC were delivered (pϭ0.001 to pϭ0.05). Infarct volume measurements revealed an inverse relationship between HUCBC dose and damage volume, which reached significance at the higher HUCBC doses (10 7 cells, pϽ0.01; 3 to 5ϫ10 7 cells, pϽ0.05). 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.

Embolic stroke is thought to cause irreparable damage in the brain immediately adjacent to the region of reduced blood perfusion. Therefore, much of the current research focuses on treatments such as anti-inflammatory, neuroprotective, and cell replacement strategies to minimize behavioral and physiological consequences. In the present study, intravenous delivery of human umbilical cord blood cells (HUCBC) 48 h after a middle cerebral artery occlusion (MCAo) in a rat resulted in both behavioral and physiological recovery. Nissl and TUNEL staining demonstrated that many of the neurons in the core were rescued, indicating that while both necrotic and apoptotic cell death occur in ischemia, it is clear that apoptosis plays a larger role than first anticipated. Further, immunohistochemical and histochemical analysis showed a diminished and/ or lack of granulocyte and monocyte infiltration and astrocytic and microglial activation in the parenchyma in animals treated with HUCBC 48 h poststroke. Successful treatment at this time point should offer encouragement to clinicians that a therapy with a broader window of efficacy may soon be available to treat stroke.

Umbilical cord blood (UCB) banking has become a new obstetrical trend. It offers expectant parents a biological insurance policy that can be used in the event of a child or family member's life-threatening illness and puts patients in a position of control over their own treatment options. However, its graduation to conventional therapy in the clinical realm relies on breakthrough research that will prove its efficacy for a range of ailments. Expanding the multipotent cells found within the mononuclear fraction of UCB so that adequate dosing can be achieved, effectively expanding desired cells ex vivo, establishing its safety and limitations in HLA-mismatched recipients, defining its mechanisms of action, and proving its utility in a wide variety of both rare and common illnesses and diseases are a few of the challenges left to tackle. Nevertheless, the field is moving fast and new UCB-based therapies are on the horizon.