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Stem Cell Reports. 2017 Feb 14;8(2):235-248. doi: 10.1016/j.stemcr.2016.12.019.

HuCNS-SC Human NSCs Fail to Differentiate, Form Ectopic Clusters, and Provide No Cognitive Benefits in a Transgenic Model of Alzheimer's Disease.

Author information

1
Department of Neurobiology & Behavior, University of California Irvine, 845 Health Sciences Road, 3200 Gross Hall, Irvine, CA 92697, USA; Sue & Bill Gross Stem Cell Research Center, University of California Irvine, 845 Health Sciences Road, 3200 Gross Hall, Irvine, CA 92697, USA; Institute for Memory Impairments & Neurological Disorders, University of California Irvine, 845 Health Sciences Road, 3200 Gross Hall, Irvine, CA 92697, USA.
2
Institute for Memory Impairments & Neurological Disorders, University of California Irvine, 845 Health Sciences Road, 3200 Gross Hall, Irvine, CA 92697, USA.
3
Sue & Bill Gross Stem Cell Research Center, University of California Irvine, 845 Health Sciences Road, 3200 Gross Hall, Irvine, CA 92697, USA; Institute for Memory Impairments & Neurological Disorders, University of California Irvine, 845 Health Sciences Road, 3200 Gross Hall, Irvine, CA 92697, USA; Department of Pathology & Laboratory Medicine, University of California Irvine, 845 Health Sciences Road, 3200 Gross Hall, Irvine, CA 92697, USA.
4
Department of Neurobiology & Behavior, University of California Irvine, 845 Health Sciences Road, 3200 Gross Hall, Irvine, CA 92697, USA; Sue & Bill Gross Stem Cell Research Center, University of California Irvine, 845 Health Sciences Road, 3200 Gross Hall, Irvine, CA 92697, USA; Institute for Memory Impairments & Neurological Disorders, University of California Irvine, 845 Health Sciences Road, 3200 Gross Hall, Irvine, CA 92697, USA. Electronic address: mblurton@uci.edu.

Abstract

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, we 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.

KEYWORDS:

Alzheimer's disease; HuCNS-SC; NSC; cognition; dementia; hippocampus; stem cells; translation; transplantation; β-amyloid

Comment in

PMID:
28199828
PMCID:
PMC5312253
DOI:
10.1016/j.stemcr.2016.12.019
[Indexed for MEDLINE]
Free PMC Article

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