Evidence map›Paper›PMID 24626225›Full record

ArticlePloS one2014

A stem-cell based bioassay to critically assess the pathology of dysfunctional neuromuscular junctions.

Peter H Chipman, Ying Zhang, Victor F Rafuse

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

18 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Optimization of Application-Driven Development ofTissue engineering. Part B, Reviews · 2022
    Review
  3. Review
  4. Review
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  6. Review
  7. Advanced biosystems · 2019
    Article
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  16. Review
  17. Motoneurons derived from induced pluripotent stem cells develop mature phenotypes typical of endogenous spinal motoneurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015
    Article
  18. Article
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

3 authors at 1 institution in 1 country.

Peter H ChipmanDepartment of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
Ying ZhangDepartment of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada; Brain Repair Centre, Life Science Research Centre, Halifax, Nova Scotia, Canada.
Victor F RafuseDepartment of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Brain Repair Centre, Life Science Research Centre, Halifax, Nova Scotia, Canada.
Dalhousie University · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Pluripotent stem cells can be directed to differentiate into motor neurons and assessed for functionality in vitro. An emerging application of this technique is to model genetically inherited diseases in differentiated motor neurons and to screen for new therapeutic targets. The neuromuscular junction (NMJ) is essential to the functionality of motor neurons and its dysfunction is a primary hallmark of motor neuron disease. However, mature NMJs that possess the functional and morphological characteristics of those formed in vivo have so far not been obtained in vitro. Here we describe the generation and analysis of mature NMJs formed between embryonic stem cell-derived motor neurons (ESCMNs) and primary myotubes. We compared the formation and maturation of NMJs generated by wild-type (NCAM+/+) ESCMNs to those generated by neural cell adhesion molecule null (NCAM-/-) ESCMNs in order to definitively test the sensitivity of this assay to identify synaptic pathology. We find that co-cultures using NCAM-/- ESCMNs replicate key in vivo NCAM-/- phenotypes and reveal that NCAM influences neuromuscular synaptogenesis by controlling the mode of synaptic vesicle endocytosis. Further, we could improve synapse formation and function in NCAM-/- co-cultures by chronic treatment with nifedipine, which blocks an immature synaptic vesicle recycling pathway. Together, our results demonstrate that this ESCMN/myofiber co-culture system is a highly sensitive bioassay for examining molecules postulated to regulate synaptic function and for screening therapeutics that will improve the function of compromised NMJs.

Indexed as

AnimalsBiological AssayCalcium ChannelsCD56 AntigenCell Adhesion MoleculesCell DifferentiationChick EmbryoCoculture TechniquesElectrophysiological PhenomenaEmbryonic Stem CellsEndocytosisFemaleMiceMice, TransgenicMotor NeuronsMuscle Fibers, SkeletalCalcium ChannelsCD56 AntigenCell Adhesion MoleculesNcam1 protein, mouseNifedipine

Identifiers

PMID24626225
PMCPMC3953473
OpenAlexW1970062723

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.