Journal
STEM CELL REPORTS
Volume 8, Issue 2, Pages 235-248Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2016.12.019
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Funding
- NIH [RF1AG048099, P50 AG016573]
- Alzheimer's Association [BFG-14-317000]
- NIA [T32 AG00096-30]
- NINDS [T32 NS082174-01]
- NIH Shared Instrumentation [OD01042]
- departmental start-up funds
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Transplantationofneural stemcells (NSCs) canimprove cognition in animal models of Alzheimer's disease (AD). However, AD is a protracted disorder, and prior studies have examined only short- termeffects. We therefore used an immune- deficientmodel of AD(Rag-5xfADmice) 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 insurvivalormigrationinresponse tob-amyloidpathology. 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-termmodels.
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