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

• Published in: Stroke (1970) Vol. 32; no. 11; pp. 2682 - 2688
• Main Authors: JIELI CHEN, SANBERG, Paul R, YI LI, LEI WANG, MEI LU, WILLING, Allison E, SANCHEZ-RAMOS, Juan, CHOPP, Michael
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.11.2001; American Heart Association, Inc
• Subjects: Animals; Behavior, Animal; Biological and medical sciences; Brain - cytology; Brain Ischemia - physiopathology; Cell Differentiation; Cell Extracts - pharmacology; Cell Survival; Chemotaxis - drug effects; Cord Blood Stem Cell Transplantation - methods; Fetal Blood - cytology; Fetal Blood - physiology; Humans; Infarction, Middle Cerebral Artery - physiopathology; Infarction, Middle Cerebral Artery - psychology; Infarction, Middle Cerebral Artery - therapy; Infusions, Intravenous; Male; Medical sciences; Neurology; Rats; Rats, Wistar; Stroke - physiopathology; Stroke - psychology; Stroke - therapy; Vascular diseases and vascular malformations of the nervous system; Human origin; Nervous system diseases; Stroke; Intravenous administration; Rat; Rodentia; Middle cerebral artery; Cardiovascular disease; Chemotaxis; Blood; Cerebral disorder; Behavioral disorder; Vascular disease; Vertebrata; Mammalia; Treatment; Animal; Central nervous system disease; Umbilical cord; Cerebrovascular disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/hs1101.098367

Human umbilical cord blood cells (HUCBC) are rich in stem 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 ischemic brain tissue extract selectively induces chemotaxis of HUCBC in vitro. Adult male Wistar rats were subjected to transient (2-hour) middle cerebral artery occlusion (MCAO). Experimental groups were as follows: group 1, MCAO alone (n=5); group 2, 3x10(6) HUCBC injected into tail vein at 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, 3x10(6) HUCBC injected into tail vein at 7 days after MCAO (n=5). Rats of groups 3, 4, and 5 were killed at 35 days after MCAO. Behavioral tests (rotarod and Modified Neurological Severity Score [mNSS]) were performed. Immunohistochemical staining was used to identify cells derived from HUCBC. Chemotactic activity of ischemia brain tissue extracts toward HUCBC at different time points was evaluated in vitro. 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 only on the mNSS (P<0.05). Some HUCBC were reactive for the astrocyte marker glial fibrillary acidic protein and the neuronal markers NeuN and microtubule-associated protein 2. In vitro, significant HUCBC migration activity was present at 24 hours after MCAO (P<0.01) compared with normal brain tissue. Intravenously administered HUCBC enter brain, survive, migrate, and improve functional recovery after stroke. HUCBC transplantation may provide a cell source to treat stroke.