Neurotherapeutic effect of cord blood derived CD45+ hematopoietic cells in mice after traumatic brain injury

Hadar Arien-Zakay, Galit Gincberg, Arnon Nagler, Gadi Cohen, Sigal Liraz-Zaltsman, Victoria Trembovler, Alexander G. Alexandrovich, Ilan Matok, Hanan Galski, Uriel Elchalal, Peter I. Lelkes, Philip Lazarovici*, Esther Shohami

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageAmerican English
Pages (from-to)1405-1416
Number of pages12
JournalJournal of Neurotrauma
Issue number16
StatePublished - 15 Aug 2014


  • brain trauma
  • cell transplantation
  • cord blood
  • neurotherapy


Dive into the research topics of 'Neurotherapeutic effect of cord blood derived CD45+ hematopoietic cells in mice after traumatic brain injury'. Together they form a unique fingerprint.

Cite this