title: Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular Hemorrhage.
abstract: We recently showed that intraventricular transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuated posthemorrhagic hydrocephalus (PHH) and brain injury after severe intraventricular hemorrhage (IVH) in newborn rat pups. The purpose of this study was to optimize the timing of MSC transplantation for severe IVH. Severe IVH was induced by injecting 100 µl of blood into each ventricle of Sprague-Dawley rats on postnatal day 4 (P4). Human UCB-derived MSCs (1 × 10(5) cells in 10 µl of normal saline) were transplanted intraventricularly under stereotaxic guidance either early at P6 or late at P11. Serial brain MRIs and behavioral function tests, such as negative geotaxis and rotarod tests, were performed. At P32, brain tissue samples were obtained for histological and biochemical analyses. Intracerebroventricular transplantation of MSCs significantly attenuated the development of PHH, behavioral impairment, increased apoptosis and astrogliosis, reduced corpus callosum thickness and brain myelination, and upregulated inflammatory cytokines including interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) at P6 but not at P11 after induction of severe IVH. Intracerebroventricular transplantation of human UCB-derived MSCs attenuated PHH and brain injury after severe IVH in newborn rats in a time-dependent manner. Significant neuroprotection was only demonstrated when administered early at 2 days after induction but not late at 7 days after induction of severe IVH.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won Soon
authors.initials: WS
authors.lastname: Park
authors.forename: Se In
authors.initials: SI
authors.lastname: Sung
authors.forename: So Yoon
authors.initials: SY
authors.lastname: Ahn
authors.forename: Dong Kyung
authors.initials: DK
authors.lastname: Sung
authors.forename: Geun Ho
authors.initials: GH
authors.lastname: Im
authors.forename: Hye Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Choi
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Chang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death; D002543:Cerebral Hemorrhage / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D003337:Corpus Callosum / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009186:Myelin Sheath / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins