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Record W2802378500 · doi:10.1016/j.celrep.2018.03.091

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering

2018· article· en· W2802378500 on OpenAlexfundno aff
Sara M. Maffioletti, Shilpita Sarcar, A. Henderson, Ingra Mannhardt, Luca Pinton, Louise A. Moyle, Heather B. Steele-Stallard, Ornella Cappellari, Kim E. Wells, Giuliana Ferrari, Jamie S. Mitchell, Giulia E. Tyzack, Vassilios N. Kotiadis, Moustafa Khedr, Martina Ragazzi, Weixin Wang, Michael R. Duchen, Rickie Patani, Peter S. Zammit, Dominic J. Wells, Thomas Eschenhagen, Francesco Saverio Tedesco

Bibliographic record

VenueCell Reports · 2018
Typearticle
Languageen
FieldMedicine
TopicTissue Engineering and Regenerative Medicine
Canadian institutionsnot available
FundersBiotechnology and Biological Sciences Research CouncilMedical Research CouncilFundació la Marató de TV3Innovative Medicines InitiativeMedical Research Council CanadaEuropean CommissionGlaxoSmithKline AustraliaServierNational Institute for Health and Care ResearchEuropean Federation of Pharmaceutical Industries and AssociationsMuscular Dystrophy UKWellcome TrustNational Institutes of Health
KeywordsInduced pluripotent stem cellSkeletal muscleMyocyteRegenerative medicineMuscular dystrophyBiologyDuchenne muscular dystrophyMyogenesisCell biologyStem cellAnatomyEmbryonic stem cellGenetics

Abstract

fetched live from OpenAlex

Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.252
Teacher spread0.235 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations323
Published2018
Admission routes1
Has abstractyes

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