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2011 | 71 | 1 |
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Systemic treatment of focal brain injury in the rat by human umbilical cord blood cells being at different level of neural commitment

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The aim of the study was to evaluate therapeutic effectiveness of intra-arterial infusion of human umbilical cord blood (HUCB) derived cells at different stages of their neural conversion. Freshly isolated mononuclear cells (D-0), neurally directed progenitors (D-3) and neural-like stem cells derived from umbilical cord blood (NSC) were compared. Focal brain damage was induced in rats by stereotactic injection of ouabain into dorsolateral striatum Three days later 107 of different subsets of HUCB cells were infused into the right internal carotid artery. Following surgery rats were housed in enriched environment for 30 days. Behavioral assessment consisted of tests for sensorimotor deficits (walking beam, rotarod, vibrissae elicited forelimb placing, apomorphine induced rotations), cognitive impairments (habit learning and object recognition) and exploratory behavior (open field). Thirty days after surgery the lesion volume was measured and the presence of donor cells was detected in the brain at mRNA level. At the same time immunohistochemical analysis of brain tissue was performed to estimate the local tissue response of ouabain injured rats and its modulation after HUCB cells systemic treatment. Functional effects of different subsets of cord blood cells shared substantial diversity in various behavioral tests. An additional analysis showed that D-0 HUCB cells were the most effective in functional restoration and reduction of brain lesion volume. None of transplanted cord blood derived cell fractions were detected in rat's brains at 30th day after treatment. This may suggest that the mechanism(s) underlying positive effects of HUCB derived cell may concern the other than direct neural cell supplementation. In addition increased immunoreactivity of markers indicating local cells proliferation and migration suggests stimulation of endogenous reparative processes by HUCB D-0 cell interarterial infusion.
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  • Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland
  • Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland
  • Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland
  • Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland
  • Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland
  • Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland
  • Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland
  • Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland
  • Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland
  • Ali H, Bahbahani H (2010) Umbilical cord blood stem cells - potential therapeutic tool for neural injuries and disor­ders. Acta Neurobiol Exp (Wars) 70: 316-324.
  • Benefiel AC, Dong WK, Greenough WT (2005) Mandatory "enriched" housing of laboratory animals: the need for evidence-based evaluation. ILAR J 46: 95-105.
  • Borlongan CV, Hadman M, Sanberg CD, Sanberg PR (2004) Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotec­tion in stroke. Stroke 35: 2385-2389.
  • Brouns R, De Deyn PP (2009) The complexity of neurobio- logical processes in acute ischemic stroke. Clin Neurol Neurosurg 111: 483-95.
  • Buffo A, Rite I, Tripathi P, Lepier A, Colak D, Horn AP, Mori T, Gotz M (2008) Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain. Proc Natl Acad Sci USA 105: 3581-3586.
  • Buffo A, Rolando C, Ceruti S (2010) Astrocytes in the dam­aged brain: molecular and cellular insights into their reac­tive response and healing potential. Biochem Pharmacol 79: 77-89.
  • Buzanska L, Machaj EK, Zablocka B, Pojda Z, Domanska- Janik K (2002) Human cord blood-derived cells attain neu­ronal and glial features in vitro. J Cell Sci 115: 2131-2138.
  • Chen J, Sanberg PR, Li Y, Wang L, Lu M, Willing AE, Sanchez-Ramos J, Chopp M (2001) Intravenous adminis­tration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke 32: 2682-2688.
  • Domanska-Janik K, Habich A, Sarnowska A, Janowski M (2006) Neural commitment of cord blood stem cells (HUCB-NSC/NP): therapeutic perspectives. Acta Neurobiol Exp (Wars) 66: 279-291.
  • Drai D, Golani I (2001) SEE: a tool for the visualization and analysis of rodent exploratory behavior. Neurosci Biobehav Rev 25: 409-426.
  • Fitch MT, Silver J (2008) CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regen­eration failure. Exp Neurol 209: 294-301.
  • Gornicka-Pawlak E, Jablolnska A, Chylinski A, Domanska-Janik K (2009) Housing conditions influ­ence motor functions and exploratory behavior fol­lowing focal damage of the rat brain. Acta Neurobiol Exp (Wars) 69: 62-72.
  • Gotts JE, Chesselet MF (2005) Migration and fate of newly born cells after focal cortical ischemia in adult rats. J Neurosci Res 80: 160-171.
  • Habich A, Jurga M, Markiewicz I, Lukomska B, Bany- Laszewicz U, Domanska-Janik K (2006) Early appear­ance of stem/progenitor cells with neural-like characteris­tics in human cord blood mononuclear fraction cultured in vitro. Exp Hematol 34: 914-925.
  • Hampton DW, Rhodes KE, Zhao C, Franklin RJ, Fawcett JW (2004) The responses of oligodendrocyte precursor cells, astrocytes and microglia to a cortical stab injury, in the brain. Neuroscience 127: 813-820.
  • Hicks A, Jolkkonen J (2009) Challenges and possibilities of intravascular cell therapy in stroke. Acta Neurobiol Exp (Wars) 69: 1-11.
  • Hicks A, Schallert T, Jolkkonen J (2009) Cell-based thera­pies and functional outcome in experimental stroke. Cell Stem Cell 5: 139-140.
  • Jablonska A, Kozlowska H, Markiewicz I, Domanska-Janik K, Lukomska B (2010) Transplantation of neural stem cells derived from human cord blood to the brain of adult and neonatal rats. Acta Neurobiol Exp (Wars) 70: 337­350.
  • Janowski M, Date I (2009) Systemic neurotransplantation-a problem-oriented systematic review. Rev Neurosci 20: 39-60.
  • Janowski M, Gornicka-Pawlak E, Kozlowska H, Domanska- Janik K, Gielecki J, Lukomska B (2008) Structural and functional characteristic of a model for deep-seated lacu­nar infarct in rats. J Neurol Sci 273: 40-48.
  • Kernie SG, Parent JM (2010) Forebrain neurogenesis after focal Ischemic and traumatic brain injury. Neurobiol Dis 37: 267-274.
  • Lappalainen RS, Narkilahti S, Huhtala T, Liimatainen T, Suuronen T, Narvanen A, Suuronen R, Hovatta O, Jolkkonen J (2008) The SPECT imaging shows the accu­mulation of neural progenitor cells into internal organs after systemic administration in middle cerebral artery occlusion rats. Neurosci Lett 440: 246-250.
  • Lewejohann L, Reinhard C, Schrewe A, Brandewiede J, Haemisch A, Gortz N, Schachner M, Sachser N (2006) Environmental bias? Effects of housing conditions, labo­ratory environment and experimenter on behavioral tests. Genes Brain Behav 5: 64-72.
  • Li L, Harms KM, Ventura PB, Lagace DC, Eisch AJ, Cunningham LA (2010) Focal cerebral ischemia induces a multilineage cytogenic response from adult subventric- ular zone that is predominantly gliogenic. Glia 58: 1610-1619.
  • Li Y, Chopp M (1999) Temporal profile of nestin expression after focal cerebral ischemia in adult rat. Brain Res 838: 1-10.
  • Macias M (2008) Injury induced dendritic plasticity in the mature central nervous system. Acta Neurobiol Exp (Wars) 68: 334-346.
  • Mäkinen S, Kekarainen T, Nystedt J, Liimatainen T, Huhtala T, Närvänen A, Laine J, Jolkkonen J (2006) Human umbilical cord blood cells do not improve sensorimotor or cognitive outcome following transient middle cerebral artery occlusion in rats. Brain Res 1123: 207-215.
  • Park DH, Borlongan CV, Willing AE, Eve DJ, Cruz LE, Sanberg CD, Chung YG, Sanberg PR (2009) Human umbilical cord blood cell grafts for brain ischemia. Cell Transplant. 18: 985-998.
  • Park DH, Eve DJ, Chung YG, Sanberg PR (2010) Regenerative medicine for neurological disorders. ScientificWorldJournal 16: 470-489.
  • Pham TM, Winblad B, Granholm AC, Mohammed AH (2002) Environmental influences on brain neurotrophins in rats. Pharmacol Biochem Behav 73: 167-175.
  • Posmantur RM, Newcomb JK, Kampfl A, Hayes RL (2000) Light and confocal microscopic studies of evolutionary changes in neurofilament proteins following cortical impact injury in the rat. Exp Neurol 161: 15-26.
  • Thored P, Arvidsson A, Cacci E, Ahlenius H, Kallur T, Darsalia V, Ekdahl CT, Kokaia Z, Lindvall O (2006) Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 24: 739­747.
  • Thored P, Wood J, Arvidsson A, Cammenga J, Kokaia Z, Lindvall O (2007) Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke. Stroke 38: 3032­3039.
  • Veldhuis WB, van der Stelt M, Delmas F, Gillet B, Veldink GA, Vliegenthart JF, Nicolay K, Bär PR (2003) In vivo excitotoxicity induced by ouabain, a Na+/K+-ATPase inhibitor. J Cereb Blood Flow Metab 23: 62-74.
  • Vendrame M, Cassady J, Newcomb J, Butler T, Pennypacker KR, Zigova T, Sanberg CD, Sanberg PR, Willing AE (2004) Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral defi­cits and reduces infarct volume. Stroke 35: 2390-2395.
  • Vendrame M, Gemma C, de Mesquita D, Collier L, Bickford PC, Sanberg CD, Sanberg PR, Pennypacker KR, Willing AE (2005) Anti-inflammatory effects of human cord blood cells in a rat model of stroke. Stem Cells Dev 14: 595-604.
  • Xiao J, Nan Z, Motooka Y, Low WC (2005) Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury. Stem Cells Dev 14: 722-733.
  • Yamashita T, Ninomiya M, Hernández Acosta P, García- Verdugo JM, Sunabori T, Sakaguchi M, Adachi K, Kojima T, Hirota Y, Kawase T, Araki N, Abe K, Okano H, Sawamoto K (2006) Subventricular zone-derived neuro- blasts migrate and differentiate into mature neurons in the post-stroke adult striatum. J Neurosci 26: 6627-36.
  • Zawadzka M, Lukasiuk K, Machaj EK, Pojda Z, Kaminska B (2009) Lack of migration and neurological benefits after infusion of umbilical cord blood cells in ischemic brain injury. Acta Neurobiol Exp (Wars) 69: 46-51.
  • Zhang R, Zhang Z, Wang L, Wang Y, Gousev A, Zhang L, Ho KL, Morshead C, Chopp M (2004) Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats. J Cereb Blood Flow Metab 24: 441-448.
  • Zhang RL, Zhang ZG, Chopp M (2008) Ischemic stroke and neurogenesis inthe subventricularzone.Neuropharmacology. 55: 345-352.
  • Zhao LR, Nam SC (2007) Multiphoton microscope imaging: the behavior of neural progenitor cells in the rostral migratory stream. Neurosci Lett 425: 83-88.
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