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HuCNS-SC human NSCs fail to differentiate, form ectopic clusters, and provide no cognitive benefits in a transgenic model of Alzheimer's disease


Year of Publication:
Contact PI Name:
Mathew Blurton-Jones
Contact PI Affiliation:
Department of Neurobiology and Behavior, University of California Irvine, Irvine, California, USA
Samuel E. Marsh, Stephen T. Yeung, Maria Torres, Lydia Lau, Joy L. Davis, Edwin S. Monuki, Wayne W. Poon
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Alzheimer's Association
National Institute of Neurological Disorders and Stroke (NINDS)
Study Goal and Principal Findings:

Transplantation of neural stem cells (NSCs) can improve cognition in animal models of Alzheimer's disease (AD). However, AD is a protracted disorder, and prior studies have examined only short-term effects. We therefore used an immune-deficient model of AD (Rag-5xfAD mice) to examine long-term transplantation of human NSCs (StemCells Inc.; HuCNS-SCs). Five months after transplantation, HuCNS-SCs had engrafted and migrated throughout the hippocampus and exhibited no differences in survival or migration in response to β-amyloid pathology. Despite robust engraftment, HuCNS-SCs failed to terminally differentiate and over a quarter of the animals exhibited ectopic human cell clusters within the lateral ventricle. Unlike prior short-term experiments with research-grade HuCNS-SCs, was also found no evidence of improved cognition, no changes in brain-derived neurotrophic factor, and no increase in synaptic density. These data, while disappointing, reinforce the notion that individual human NSC lines need to be carefully assessed for efficacy and safety in appropriate long-term models.

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:

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
Y Maze
Elevated Plus Maze
beta Amyloid Deposits
beta Amyloid Load
Brain-Derived Neurotrophic Factor (BDNF)
Brain-beta Amyloid Peptide-Total
Immature Neurons
Immature Oligodendrocytes
Synaptic Density
Synaptic Markers
Cell Survival
Cell Differentiation
Cell Migration
Glial Fibrillary Acidic Protein (GFAP)
Postsynaptic Density Protein 95 (PSD95)
Neuronal Cell Number
Cell Biology
Engrafted Stem Cells