title: Effect of human umbilical cord blood derived lineage negative stem cells transplanted in amyloid-β induced cognitive impaired mice.
abstract: Alzheimer's disease (AD) is pathologically characterized by extracellular deposition of insoluble amyloid-β (Aβ) plaques and intracellular tangles made up of phosphorylated tau in brain. Several therapeutic approaches are being carried out in animal AD models for testing their safety and efficacy in altering disease pathology and behavioral deficits. Very few studies have examined the effect of human umbilical cord blood (hUCB) derived stem cells in degenerative disease models despite growing number of cord blood banks worldwide. Here we have examined the therapeutic efficacy of hUCB derived lineage negative (Lin -ve) stem cells in alleviating behavioral and neuropathological deficits in a mouse model of cognitive impairment induced by bilateral intrahippocampal injection of Aβ-42. Lin -ve cells were transplanted at two doses (50,000 and 100,000) at the site of injury and examined at 10 and 60 days post transplantation for rescue of memory deficits. These cells were found to ameliorate cognitive impairment in 50,000-60 days and 100,000-10 days groups whereas, 50,000-10 days and 100,000-60 days groups could not exert any significant improvement. Further, mice showing spatial memory improvement were mediated by up-regulation of BDNF, CREB and also by concomitant down regulation of Fas-L in their brain. The transplanted cells were found in the host tissue and survived up to 60 days without expressing markers of neuronal differentiation or reducing Aβ burden in mouse brain. We suggest that these undifferentiated cells could exert neuroprotective effects either through inhibiting apoptosis and/or trophic effects in the brain.
authors.affiliation: Neuroscience Research Lab, Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Avijit
authors.initials: A
authors.lastname: Banik
authors.affiliation: Neuroscience Research Lab, Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Sudesh
authors.initials: S
authors.lastname: Prabhakar
authors.affiliation: Department of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Jasvinder
authors.initials: J
authors.lastname: Kalra
authors.affiliation: Neuroscience Research Lab, Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address: akshay1anand@rediffmail.com.
authors.forename: Akshay
authors.initials: A
authors.lastname: Anand
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides; D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D003072:Cognition Disorders / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D010446:Peptide Fragments; D065852:Spatial Memory / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Amyloid-β; BDNF; CREB; Lineage negative; Umbilical cord blood