Multiple low-dose infusions of human umbilical cord blood cells improve cognitive impairments and reduce amyloid-β-associated neuropathology in Alzheimer mice
| Autor: | Takashi Mori, Jared Ehrhart, Donna Darlington, Nicole Kuzmin-Nichols, Cyndy D. Sanberg, Paul R. Sanberg, Hua-Dong Zhou, Jun Tan, Huayan Hou, Juan Deng, Brian Giunta |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Pathology medicine.medical_specialty Population Mice Transgenic Plaque Amyloid Neuropathology Biology Umbilical cord Rotarod performance test Cell therapy Amyloid beta-Protein Precursor Mice Cognition Original Research Reports Alzheimer Disease medicine Dementia Animals Humans Infusions Parenteral education Maze Learning Cells Cultured education.field_of_study Microglia Brain Cell Biology Hematology Recovery of Function medicine.disease medicine.anatomical_structure Memory Short-Term Motor Skills Rotarod Performance Test Immunology Leukocyte Common Antigens Female Cord Blood Stem Cell Transplantation Alzheimer's disease Developmental Biology |
| Zdroj: | Stem cells and development. 22(3) |
| ISSN: | 1557-8534 |
| Popis: | Alzheimer's disease (AD) is the most common progressive age-related dementia in the elderly and the fourth major cause of disability and mortality in that population. The disease is pathologically characterized by deposition of β-amyloid plaques neurofibrillary tangles in the brain. Current strategies for the treatment of AD are symptomatic only. As such, they are less than efficacious in terms of significantly slowing or halting the underlying pathophysiological progression of the disease. Modulation by cell therapy may be new promising disease-modifying therapy. Recently, we showed reduction in amyloid-β (Aβ) levels/β-amyloid plaques and associated astrocytosis following low-dose infusions of mononuclear human umbilical cord blood cells (HUCBCs). Our current study extended our previous findings by examining cognition via (1) the rotarod test, (2) a 2-day version of the radial-arm water maze test, and (3) a subsequent observation in an open pool platform test to characterize the effects of monthly peripheral HUCBC infusion (1×10(6) cells/μL) into the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) from 6 to 12 months of age. We show that HUCBC therapy correlates with decreased (1) cognitive impairment, (2) Aβ levels/β-amyloid plaques, (3) amyloidogenic APP processing, and (4) reactive microgliosis after a treatment of 6 or 10 months. As such, this report lays the groundwork for an HUCBC therapy as potentially novel alternative to oppose AD at the disease-modifying level. |
| Databáze: | OpenAIRE |
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