Evidence map›Paper›PMID 31084710›Full record

ArticleeLife2019

A 3D culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction.

Mohsen Afshar Bakooshli, Ethan S Lippmann, Ben Mulcahy, Nisha Iyer, Christine T Nguyen, Kayee Tung, Bryan A Stewart, Hubrecht van den Dorpel, Tobias Fuehrmann, Molly Shoichet and 7 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 1 pooled it
15.7field-weighted citation impact, top 1% 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

149 citing papers in PubMed, 1 synthesis or guideline pooled it, 268 citations in OpenAlex.

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89 more citing papers are in PubMed but not listed here.

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

17 authors at 7 institutions in 5 countries.

Mohsen Afshar BakooshliDonnelly Centre, University of Toronto, Toronto, Canada.
Ethan S LippmannDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, United States.
Ben MulcahyLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.ORCID 0000-0002-3336-245X
Nisha IyerDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, United States.
Christine T NguyenDepartment of Cell and Systems Biology, University of Toronto, Toronto, Canada.
Kayee TungDepartment of Surgery, University of Toronto, Toronto, Canada.
Bryan A StewartDepartment of Cell and Systems Biology, University of Toronto, Toronto, Canada.ORCID 0000-0003-2520-3632
Hubrecht van den DorpelInstitute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
Tobias FuehrmannDonnelly Centre, University of Toronto, Toronto, Canada.
Molly ShoichetDonnelly Centre, University of Toronto, Toronto, Canada.
Anne BigotINSERM, Association Institut de Myologie, Centre de Recherche en Myologie, Sorbonne Universite, Paris, France.
Elena PegoraroDepartment of Neuroscience, University of Padova, Padova, Italy.
Henry AhnDepartment of Surgery, University of Toronto, Toronto, Canada.
Howard GinsbergInstitute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
Mei ZhenLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.ORCID 0000-0003-0086-9622
Randolph Scott AshtonDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, United States.ORCID 0000-0002-6842-7022
Penney M GilbertDonnelly Centre, University of Toronto, Toronto, Canada.ORCID 0000-0001-5509-9616
University of New Brunswick · CAUniversity of Toronto · CAUniversity of Wisconsin–Madison · USMount Sinai Hospital · CAInserm · FRSt. Michael's Hospital · CAUniversity of Padua · IT

Funding

High-Throughput Modeling of ALS Using iPSC-Derived Neural Tube MicroarraysR33NS082618 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI ASHTON, RANDOLPH S · 2017 to 2018
$779k
High-Throughput Modeling of ALS Using iPSC-Derived Neural Tube MicroarraysR21NS082618 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI ASHTON, RANDOLPH S · 2014 to 2015
$348k
Modeling spinal cord axis patterning with human pluripotent stem cellsF32NS083291 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI LIPPMANN, ETHAN · 2013 to 2015
$91k
AFM-Téléthon MyobankAFM-Téléthon Network of Genetic Biobanks (GTB12001D)Burroughs Wellcome Fund Innovation in Regulatory Science AwardCanada First Research Excellence Fund 'Medicine by Design' OMNI-2017-01Canada Foundation for Innovation 31390Canada Research Chairs 950-231201CIHR Foundation Scheme 15427Natural Sciences and Engineering Research Council of Canada CREATE TOePNatural Sciences and Engineering Research Council of Canada RGPIN-2017-06738Natural Sciences and Engineering Research Council of Canada RGPIN 435724-13NIH HHS 1F32NS083291-01A1NIH HHS R21NS082618NINDS NIH HHS F32 NS083291NINDS NIH HHS R21 NS082618NINDS NIH HHS R33 NS082618Ontario Institute for Regenerative Medicine OMNI-2017-01Ontario Research Fund 31390University of Toronto Ontario Graduate ScholarshipUniversity of Toronto Faculty of Medicine Deans FundU.S. Environmental Protection Agency STAR center grant 83573701
6 · The paper itself

Abstract

Two-dimensional (2D) human skeletal muscle fiber cultures are ill-equipped to support the contractile properties of maturing muscle fibers. This limits their application to the study of adult human neuromuscular junction (NMJ) development, a process requiring maturation of muscle fibers in the presence of motor neuron endplates. Here we describe a three-dimensional (3D) co-culture method whereby human muscle progenitors mixed with human pluripotent stem cell-derived motor neurons self-organize to form functional NMJ connections. Functional connectivity between motor neuron endplates and muscle fibers is confirmed with calcium imaging and electrophysiological recordings. Notably, we only observed epsilon acetylcholine receptor subunit protein upregulation and activity in 3D co-cultures. Further, 3D co-culture treatments with myasthenia gravis patient sera shows the ease of studying human disease with the system. Hence, this work offers a simple method to model and evaluate adult human NMJ de novo development or disease in culture.

Indexed as

Coculture TechniquesHumansMotor NeuronsMuscle CellsMuscle, SkeletalNeuromuscular JunctionOrgan Culture Techniques3D co-cultureacetylcholine receptor subunit epsilondevelopmental biologyhumanmotor neuronmyasthenia gravisneuromuscular junctionregenerative medicineskeletal musclestem cells

Identifiers

PMID31084710
PMCPMC6516829
OpenAlexW2945467118

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.