title: Repeated administrations of human umbilical cord blood cells improve disease outcomes in a mouse model of Sanfilippo syndrome type III B.
abstract: Sanfilippo syndrome type III B (MPS III B) is an inherited disorder characterized by a deficiency of α-N-acetylglucosaminidase (Naglu) enzyme leading to accumulation of heparan sulfate in lysosomes and severe neurological deficits. We have previously shown that a single administration of human umbilical cord mononuclear cells (hUCB MNCs) into Naglu knockout mice decreased behavioral abnormalities and tissue pathology. In this study, we tested whether repeated doses of hUCB MNCs would be more beneficial than a single dose of cells. Naglu mice at 3 months of age were randomly assigned to either a Media-only group or one of three hUCB MNC treatment groups--single low dose (3 × 10(6) cells), single high dose (1.8 × 10(7) cells), or multiple doses (3 × 10(6) cells monthly for 6 months) delivered intravenously; cyclosporine was injected intraperitoneally to immune suppress the mice for the duration of the study. An additional control group of wild-type mice was also used. We measured anxiety in an open field test and cognition in an active avoidance test prior to treatment and then at monthly intervals for 6 months. hUCB MNCs restored normal anxiety-like behavior in these mice (p < 0.001). The repeated cell administrations also restored hippocampal cytoarchitecture, protected the dendritic tree, decreased GM3 ganglioside accumulation, and decreased microglial activation, particularly in the hippocampus and cortex. These data suggest that the neuroprotective effect of hUCB MNCs can be enhanced by repeated cell administrations.
authors.affiliation: Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Willing
authors.forename: Svitlana N
authors.initials: SN
authors.lastname: Garbuzova-Davis
authors.forename: Olga
authors.initials: O
authors.lastname: Zayko
authors.forename: Hiranya M
authors.initials: HM
authors.lastname: Derasari
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Rawls
authors.forename: Chris R
authors.initials: CR
authors.lastname: James
authors.forename: Ron F
authors.initials: RF
authors.lastname: Mervis
authors.forename: Cyndy D
authors.initials: CD
authors.lastname: Sanberg
authors.forename: Nicole
authors.initials: N
authors.lastname: Kuzmin-Nichols
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000118:Acetylglucosaminidase / Q000172:deficiency / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000150:complications / Q000503:physiopathology; D001362:Avoidance Learning; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D002452:Cell Count; D003071:Cognition; D036101:Cord Blood Stem Cell Transplantation; D003712:Dendrites / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005679:G(M3) Ganglioside / Q000378:metabolism; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology; D009084:Mucopolysaccharidosis III / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D010641:Phenotype; D016896:Treatment Outcome; D014470:Umbilical Cord / Q000166:cytology*; D014556:Urine
chemical_list: D005679:G(M3) Ganglioside; C033079:alpha-N-acetyl-D-glucosaminidase; D000118:Acetylglucosaminidase