Evidence map›Paper›PMID 36650030›Full record

ArticleAdvanced materials (Deerfield Beach, Fla.)2023

Bioengineered 3D Skeletal Muscle Model Reveals Complement 4b as a Cell-Autonomous Mechanism of Impaired Regeneration with Aging.

Kai Wang, Stephen H Smith, Hirotaka Iijima, Zachary R Hettinger, Adarsh Mallepally, Sanjeev G Shroff, Fabrisia Ambrosio

Open access · hybridAbstract read
In one paragraph

Article in Advanced materials (Deerfield Beach, Fla.), 2023. 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
2.9field-weighted citation impact, top 9% 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, 19 citations in OpenAlex.

  1. Article
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  4. Targeting C1q signaling in fibro-adipogenic progenitors prevents regenerative fibrosis of aged muscle.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  17. Arsenic disrupts extracellular vesicle-mediated signaling in regenerating myofibers.Toxicological sciences : an official journal of the Society of Toxicology · 2023
    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

7 authors at 2 institutions in 1 country.

Kai WangDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, USA.ORCID https://orcid.org/0000-0001-8447-6177
Stephen H SmithDepartment of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Hirotaka IijimaDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Zachary R HettingerDiscovery Center for Musculoskeletal Recovery, Schoen Adams Research Institute at Spaulding, Charlestown, MA, 02129, USA.
Adarsh MallepallyDepartment of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Sanjeev G ShroffDepartment of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Fabrisia AmbrosioDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, USA.ORCID https://orcid.org/0000-0002-5497-5968
University of Pittsburgh · USHarvard University · US

Funding

Physical exercise and Blood-brain communication: exosomes, Klotho and choroid plexusR01AG066198 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AMBROSIO, FABRISIA, KOLDAMOVA, RADOSVETA · 2020 to 2024
$3.8M
Role of extracellular matrix in age-related declines of muscle regenerationR01AG061005 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AMBROSIO, FABRISIA, LEDUC, PHILIP R · 2019 to 2023
$2.5M
The Anti-Aging Role of Klotho in Skeletal Muscle RegenerationR01AG052978 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AMBROSIO, FABRISIA · 2017 to 2020
$2.0M
Request for a Nikon A1 confocal microscopeS10OD019973 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WATKINS, SIMON C · 2015 to 2015
$358k
NIA NIH HHS R01AG052978NIA NIH HHS R01 AG061005NIA NIH HHS R01AG061005NIA NIH HHS R01 AG066198NIA NIH HHS R01AG066198NIH HHS 1S10OD019973
6 · The paper itself

Abstract

A mechanistic understanding of cell-autonomous skeletal muscle changes after injury can lead to novel interventions to improve functional recovery in an aged population. However, major knowledge gaps persist owing to limitations of traditional biological aging models. 2D cell culture represents an artificial environment, while aging mammalian models are contaminated by influences from non-muscle cells and other organs. Here, a 3D muscle aging system is created to overcome the limitations of these traditional platforms. It is shown that old muscle constructs (OMC) manifest a sarcopenic phenotype, as evidenced by hypotrophic myotubes, reduced contractile function, and decreased regenerative capacity compared to young muscle constructs. OMC also phenocopy the regenerative responses of aged muscle to two interventions, pharmacological and biological. Interrogation of muscle cell-specific mechanisms that contribute to impaired regeneration over time further reveals that an aging-induced increase of complement component 4b (C4b) delays muscle progenitor cell amplification and impairs functional recovery. However, administration of complement factor I, a C4b inactivator, improves muscle regeneration in vitro and in vivo, indicating that C4b inhibition may be a novel approach to enhance aged muscle repair. Collectively, the model herein exhibits capabilities to study cell-autonomous changes in skeletal muscle during aging, regeneration, and intervention.

Indexed as

Complement C4bMuscle, SkeletalAgingAnimalsMammalsMuscle ContractionMuscle Fibers, SkeletalComplement C4bbiomimetic muscle modelsdrug testinginflammationmuscle stem cellsskeletal muscle aging

Identifiers

PMID36650030
PMCPMC13175247
OpenAlexW4317359087

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.