Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats

Background and Purpose-Human umbilical cord blood cells (HUCBC) are rich in stein and progenitor cells. In this study we tested whether intravenously infused HUCBC enter brain, survive, differentiate, and improve neurological functional recovery after stroke in rats. In addition, we tested whether i schemic brain tissue extract selectively induces chemotaxis of HUCBC in vit ro. Methods-Adult male Wistar rats were subjected to transient (2-hour) middle cerebral artery occlusion (MCAO). Experimental groups were as follows: grou p 1, MCAO alone (n = 5), group 2, 3 x 10(6) HUCBC injected into tail vein a t 24 hours after MCAO (n = 6) (animals of groups 1 and 2 were killed at 14 days after MCAO); group 3, MCAO alone (n = 5); group 4, MCAO injected with PBS at 1 day after stroke (n = 8); and group 5, 3 x 10(6) HUCBC injected in to tail vein at 7 days after MCAO (n=5). Rats of groups 3, 4, and 5 were ki lled at 35 days after MCAO. Behavioral tests (rotarod and Modified Neurolog ical Severity Score [mNSS]) were performed. Immunohistochemical staining wa s used to identify cells derived from HUCBC. Chemotactic activity of ischem ia brain tissue extracts toward HUCBC at different time points was evaluate d in vitro. Results-Treatment at 24 hours after MCAO with HUCBC significantly improved functional recovery, as evidenced by the rotarod test and mNSS (P < 0.05). Treatment at 7 days after MCAO with HUCBC significantly improved function o nly on the mNSS (P < 0.05). Some HUCBC were reactive for the astrocyte mark er glial fibrillary acidic protein and the neuronal markers NeuN and microt ubule-associated protein 2. In vitro, significant HUCBC migration activity was present at 24 hours after MCAO (P < 0.01) compared with normal brain ti ssue. Conclusions-Intravenously administered HUCBC enter brain, survive, migrate, and improve functional recovery after stroke. HUCBC transplantation may pr ovide a cell source to treat stroke.