Evidence map›Paper›PMID 26744412›Full record

ArticleStem cells translational medicine2016

Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-I: A Novel Cellular Therapy for Alzheimer's Disease.

Lisa M McGinley, Erika Sims, J Simon Lunn, Osama N Kashlan, Kevin S Chen, Elizabeth S Bruno, Crystal M Pacut, Tom Hazel, Karl Johe, Stacey A Sakowski and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cells translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
6.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 78 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Lisa M McGinleyDepartment of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Erika SimsDepartment of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
J Simon LunnDepartment of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Osama N KashlanDepartment of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.
Kevin S ChenDepartment of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.
Elizabeth S BrunoDepartment of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Crystal M PacutDepartment of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Tom HazelNeuralstem, Inc., Germantown, Maryland, USA.
Karl JoheNeuralstem, Inc., Germantown, Maryland, USA.
Stacey A SakowskiA. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, Michigan, USA.
Eva L FeldmanDepartment of Neurology, University of Michigan, Ann Arbor, Michigan, USA A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, Michigan, USA efeldman@med.umich.edu.
University of Michigan · US

Funding

TRAINING IN CLINICAL AND BASIC NEUROSCIENCET32NS007222 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Henry L Paulson · 1985 to 2026
$8.0M
UM Clinical Neuroscientist Training ProgramR25NS089450 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALBIN, ROGER L · 2014 to 2023
$1.3M
NINDS NIH HHS R25 NS089450NINDS NIH HHS R25NS089450NINDS NIH HHS T32 NS007222NINDS NIH HHS T32NS07222
6 · The paper itself

Abstract

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder and a leading cause of dementia. Current treatment fails to modify underlying disease pathologies and very little progress has been made to develop effective drug treatments. Cellular therapies impact disease by multiple mechanisms, providing increased efficacy compared with traditional single-target approaches. In amyotrophic lateral sclerosis, we have shown that transplanted spinal neural stem cells (NSCs) integrate into the spinal cord, form synapses with the host, improve inflammation, and reduce disease-associated pathologies. Our current goal is to develop a similar "best in class" cellular therapy for AD. Here, we characterize a novel human cortex-derived NSC line modified to express insulin-like growth factor-I (IGF-I), HK532-IGF-I. Because IGF-I promotes neurogenesis and synaptogenesis in vivo, this enhanced NSC line offers additional environmental enrichment, enhanced neuroprotection, and a multifaceted approach to treating complex AD pathologies. We show that autocrine IGF-I production does not impact the cell secretome or normal cellular functions, including proliferation, migration, or maintenance of progenitor status. However, HK532-IGF-I cells preferentially differentiate into gamma-aminobutyric acid-ergic neurons, a subtype dysregulated in AD; produce increased vascular endothelial growth factor levels; and display an increased neuroprotective capacity in vitro. We also demonstrate that HK532-IGF-I cells survive peri-hippocampal transplantation in a murine AD model and exhibit long-term persistence in targeted brain areas. In conclusion, we believe that harnessing the benefits of cellular and IGF-I therapies together will provide the optimal therapeutic benefit to patients, and our findings support further preclinical development of HK532-IGF-I cells into a disease-modifying intervention for AD.

Indexed as

NeurogenesisAlzheimer DiseaseAnimalsCell- and Tissue-Based TherapyCell DifferentiationDisease Models, AnimalGene Expression Regulation, DevelopmentalHumansInsulin-Like Growth Factor IMiceNeural Stem CellsNeuronsSynapsesInsulin-Like Growth Factor IAlzheimer’s diseaseCellular therapyInsulin-like growth factor-INeural stem cellNeurodegenerationStem cell transplantation

Identifiers

PMID26744412
PMCPMC4807660
OpenAlexW2236941697

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.