Evidence map›Paper›PMID 30324134›Full record

ArticleScience advances2018

Microphysiological 3D model of amyotrophic lateral sclerosis (ALS) from human iPS-derived muscle cells and optogenetic motor neurons.

Tatsuya Osaki, Sebastien G M Uzel, Roger D Kamm

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

Article in Science advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
239citing papers in PubMed, 1 pooled it
28.9field-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

239 citing papers in PubMed, 1 synthesis or guideline pooled it, 406 citations in OpenAlex.

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179 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

3 authors at 3 institutions in 2 countries.

Tatsuya OsakiDepartment of Mechanical Engineering, Massachusetts Institute of Technology, 500 Technology Square, Room NE47-321, Cambridge, MA 02139, USA.ORCID 0000-0001-7174-0629
Sebastien G M UzelDepartment of Mechanical Engineering, Massachusetts Institute of Technology, 500 Technology Square, Room NE47-321, Cambridge, MA 02139, USA.
Roger D KammDepartment of Mechanical Engineering, Massachusetts Institute of Technology, 500 Technology Square, Room NE47-321, Cambridge, MA 02139, USA.ORCID 0000-0002-7232-304X
Harvard University · USMassachusetts Institute of Technology · USSingapore-MIT Alliance for Research and Technology · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease involving loss of motor neurons (MNs) and muscle atrophy, still has no effective treatment, despite much research effort. To provide a platform for testing drug candidates and investigating the pathogenesis of ALS, we developed an ALS-on-a-chip technology (i.e., an ALS motor unit) using three-dimensional skeletal muscle bundles along with induced pluripotent stem cell (iPSC)-derived and light-sensitive channelrhodopsin-2-induced MN spheroids from a patient with sporadic ALS. Each tissue was cultured in a different compartment of a microfluidic device. Axon outgrowth formed neuromuscular junctions on the muscle fiber bundles. Light was used to activate muscle contraction, which was measured on the basis of pillar deflections. Compared to a non-ALS motor unit, the ALS motor unit generated fewer muscle contractions, there was MN degradation, and apoptosis increased in the muscle. Furthermore, the muscle contractions were recovered by single treatments and cotreatment with rapamycin (a mechanistic target of rapamycin inhibitor) and bosutinib (an Src/c-Abl inhibitor). This recovery was associated with up-regulation of autophagy and degradation of TAR DNA binding protein-43 in the MNs. Moreover, administering the drugs via an endothelial cell barrier decreased the expression of P-glycoprotein (an efflux pump that transports bosutinib) in the endothelial cells, indicating that rapamycin and bosutinib cotreatment has considerable potential for ALS treatment. This ALS-on-a-chip and optogenetics technology could help to elucidate the pathogenesis of ALS and to screen for drug candidates.

Indexed as

Amyotrophic Lateral SclerosisAnimalsCalcium SignalingElectric StimulationGene ExpressionGlutamic AcidHumansInduced Pluripotent Stem CellsLab-On-A-Chip DevicesMiceMotor NeuronsMuscle ContractionMuscle Fibers, SkeletalMuscle, SkeletalNeuromuscular JunctionOptogeneticsGlutamic Acid

Identifiers

PMID30324134
PMCPMC6179377
OpenAlexW2897845597

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.