title: Use of human umbilical cord blood mononuclear cells to prevent perinatal brain injury: a preclinical study.
abstract: Cerebral palsy (CP) is the most frequent neurological disorder associated with perinatal injury of the developing brain. Major brain lesions associated with CP are white matter damage (WMD) in preterm infants and cortico-subcortical lesions in term newborns. Cell therapy is considered promising for the repair of brain damage. Human umbilical cord blood mononuclear cells (hUCB-MNCs) are a rich source of various stem cells that could be of interest in repairing perinatal brain damage. Our goal was to investigate the potential of hUCB-MNCs to prevent or repair brain lesions in an animal model of excitotoxic brain injury. We induced neonatal brain lesions using intracranial injections of ibotenate, a glutamate agonist, in 5-day-old rat pups. hUCB-MNCs were injected either intraperitoneally (i.p.) or intravenously (i.v.) soon or 24 h after ibotenate injection, and their neurological effects were assessed using histology and immunohistochemistry. hUCB-MNCs injected i.p. did not reach the systemic circulation but high amounts induced a significant systemic inflammatory response and increased the WMD induced by the excitotoxic insult. This effect was associated with a significant 40% increase in microglial activation around the white matter lesion. hUCB-MNCs injected i.v. soon or 24 h after the excitotoxic insult did not affect lesion size, microglial activation, astroglial cell density, or cell proliferation within the developing white matter or cortical plate at any concentration used. We demonstrated that hUCB-MNCs could not integrate into the developing brain or promote subsequent repair in most conditions tested. We found that the intraperitoneal injection of high amounts of hUCB-MNCs aggravated WMD and was associated with systemic inflammation.
authors.affiliation: INSERM UMR 676, Université Paris-Diderot, PRES Sorbonne Paris-Cité, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Dalous
authors.forename: Julien
authors.initials: J
authors.lastname: Pansiot
authors.forename: Hoa
authors.initials: H
authors.lastname: Pham
authors.forename: Paul
authors.initials: P
authors.lastname: Chatel
authors.forename: Céline
authors.initials: C
authors.lastname: Nadaradja
authors.forename: Irene
authors.initials: I
authors.lastname: D'Agostino
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vottier
authors.forename: Leslie
authors.initials: L
authors.lastname: Schwendimann
authors.forename: Valérie
authors.initials: V
authors.lastname: Vanneaux
authors.forename: Christiane
authors.initials: C
authors.lastname: Charriaut-Marlangue
authors.forename: Luigi
authors.initials: L
authors.lastname: Titomanlio
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: Jérôme
authors.initials: J
authors.lastname: Larghero
authors.forename: Olivier
authors.initials: O
authors.lastname: Baud
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D002470:Cell Survival; D002478:Cells, Cultured; D002547:Cerebral Palsy / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D036101:Cord Blood Stem Cell Transplantation; D016207:Cytokines / Q000097:blood; D005260:Female; D006087:Graft vs Host Reaction; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D009000:Monocytes / Q000502:physiology; D009416:Nerve Regeneration; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines