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Human neural stem cells improve cognition and promote synaptic growth in two complementary transgenic models of Alzheimer’s disease and neuronal loss


Year of Publication:
Contact PI Name:
Mathew Blurton-Jones
Contact PI Affiliation:
Department of Neurobiology and Behavior, University of California Irvine, Irvine, California, USA
Rahasson R. Ager, Joy L. Davis, Andy Agazaryan, Francisca Benavente, Wayne W. Poon, Frank M. LaFerla
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Alzheimer's Association
California Institute for Regenerative Medicine (CIRM)
Study Goal and Principal Findings:

Alzheimer’s disease (AD) is the most prevalent age-related neurodegenerative disorder, affecting over 35 million people worldwide. Pathologically, AD is characterized by the progressive accumulation of b-amyloid (Aβ) plaques and neurofibrillary tangles within the brain. Together, these pathologies lead to marked neuronal and synaptic loss and corresponding impairments in cognition. Current treatments, and recent clinical trials, have failed to modify the clinical course of AD; thus, the development of novel and innovative therapies is urgently needed. Over the last decade, the potential use of stem cells to treat cognitive impairment has received growing attention. Specifically, neural stem cell transplantation as a treatment for AD offers a novel approach with tremendous therapeutic potential. Previously was reported that intrahippocampal transplantation of murine neural stem cells (mNSCs) can enhance synaptogenesis and improve cognition in 3xTg-AD mice and the CaM/Tet-DTA model of hippocampal neuronal loss. These promising findings prompted this study to examine a human neural stem cell population, HuCNS-SC, which has already been clinically tested for other neurodegenerative disorders. In this study, is provided the first evidence that transplantation of research grade HuCNS-SCs can improve cognition in two complementary models of neurodegeneration. It was also demonstrated that HuCNS-SC cells can migrate and differentiate into immature neurons and glia and significantly increase synaptic and growth-associated markers in both 3xTg-AD and CaM/Tet- DTA mice. Interestingly, improvements in aged 3xTg-AD mice were not associated with altered Aβ or tau pathology. Rather, these findings suggest that human NSC transplantation improves cognition by enhancing endogenous synaptogenesis. Taken together, data provided the first preclinical evidence that human NSC transplantation could be a safe and effective therapeutic approach for treating AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Cell-based
Therapeutic Agent:
HuCNS-SC (Human Neural Stem Cell Population)
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Strain/Genetic Background:

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Morris Water Maze
Novel Object Recognition Test (NORT)
Activated Microglia
beta Amyloid Deposits
Tau Pathology
Brain-Detergent Soluble beta Amyloid Peptide 40
Brain-Detergent Soluble beta Amyloid Peptide 42
Brain-Detergent Insoluble beta Amyloid Peptide 40
Brain-Detergent Insoluble beta Amyloid Peptide 42
Insoluble Tau
Soluble Tau
Total Tau Protein
Glial Fibrillary Acidic Protein (GFAP)
Activated Astrocytes
Brain-beta Amyloid Deposits
Cell Differentiation
Growth Associated Protein 43 (GAP43)
Immature Oligodendrocytes
Immature Neurons
Neuronal Cell Number
Cell Biology
Engrafted Stem Cells