title: Neurotherapeutic effect of cord blood derived CD45+ hematopoietic cells in mice after traumatic brain injury.
abstract: Treatment of traumatic brain injury (TBI) is still an unmet need. Cell therapy by human umbilical cord blood (HUCB) has shown promising results in animal models of TBI and is under evaluation in clinical trials. HUCB contains different cell populations but to date, only mesenchymal stem cells have been evaluated for therapy of TBI. Here we present the neurotherapeutic effect, as evaluated by neurological score, using a single dose of HUCB-derived mononuclear cells (MNCs) upon intravenous (IV) administration one day post-trauma in a mouse model of closed head injury (CHI). Delayed (eight days post-trauma) intracerebroventricular administration of MNCs showed improved neurobehavioral deficits thereby extending the therapeutic window for treating TBI. Further, we demonstrated for the first time that HUCB-derived pan-hematopoietic CD45 positive (CD45(+)) cells, isolated by magnetic sorting and characterized by expression of CD45 and CD11b markers (96-99%), improved the neurobehavioral deficits upon IV administration, which persisted for 35 days. The therapeutic effect was in a direct correlation to a reduction in the lesion volume and decreased by pre-treatment of the cells with anti-human-CD45 antibody. At the site of brain injury, 1.5-2 h after transplantation, HUCB-derived cells were identified by near infrared scanning and immunohistochemistry using anti-human-CD45 and anti-human-nuclei antibodies. Nerve growth factor and vascular endothelial growth factor levels were differentially expressed in both ipsilateral and contralateral brain hemispheres, thirty-five days after CHI, measured by enzyme-linked immunosorbent assay. These findings indicate the neurotherapeutic potential of HUCB-derived CD45(+) cell population in a mouse model of TBI and propose their use in the clinical setting of human TBI.
authors.affiliation: 1 School of Pharmacy Institute for Drug Research, The Hebrew University of Jerusalem , Jerusalem, Israel .
authors.forename: Hadar
authors.initials: H
authors.lastname: Arien-Zakay
authors.forename: Galit
authors.initials: G
authors.lastname: Gincberg
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Gadi
authors.initials: G
authors.lastname: Cohen
authors.forename: Sigal
authors.initials: S
authors.lastname: Liraz-Zaltsman
authors.forename: Victoria
authors.initials: V
authors.lastname: Trembovler
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Alexandrovich
authors.forename: Ilan
authors.initials: I
authors.lastname: Matok
authors.forename: Hanan
authors.initials: H
authors.lastname: Galski
authors.forename: Uriel
authors.initials: U
authors.lastname: Elchalal
authors.forename: Peter I
authors.initials: PI
authors.lastname: Lelkes
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarovici
authors.forename: Esther
authors.initials: E
authors.lastname: Shohami
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000628:therapy*; D002469:Cell Separation; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D051379:Mice; D020127:Recovery of Function
chemical_list: D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
keywords: CD45+ hematopoietic cells; brain trauma; cell transplantation; cord blood; neurotherapy