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

Abstract

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.

Transduction of Neural Precursor Cells with TAT-Heat Shock Protein 70 Chaperone: Therapeutic Potential Against Ischemic Stroke after Intrastriatal and Systemic Transplantation

“…On the other hand, systemic transplantation of NPCs mediates acute neuroprotection from the luminal side of the vessels for which high intracerebral cell numbers seem to be not necessary. This observation is in line with previous reports where systemic transplantation of stem and precursor cells initiated beneficial effects despite low cell numbers or even no detectable cells within the ischemic brain [60][61][62][63].…”

Rescuing the neonatal brain from hypoxic injury with autologous cord blood

“…[89][90][91][92][93][94][95][96] Beneficial effects have generally been observed determined by behavioral improvements in most cases, but also by the reduction in lesion size in some studies. Owing to the poor survival of the transplanted cells and little evidence for neural differentiation, bystander effects have been postulated to be the main mechanisms for functional recovery after CB transplantation, including release of neurotrophic factors to stimulate endogenous neurogenesis, prevention of cell loss and immunomodulation (Figure 4).…”

Targeting the stem cell niche: squeezing blood from bones

“…Cord blood cells can be expanded in culture and induced to differentiate into cells with neural markers. 37 Recently, cord blood cells have been shown to improve functional recovery in rats that have been subjected to strokes, by middle cerebral artery occlusion. Infarct volume was reduced and behavioral performance increased when a higher dose of cells was infused.…”