Evidence map›Paper›PMID 33631652›Full record

ArticleBiomaterials2021

Astrocyte-derived extracellular vesicles enhance the survival and electrophysiological function of human cortical neurons in vitro.

Changho Chun, Alec S T Smith, Hyejin Kim, Dana S Kamenz, Jung Hyun Lee, Jong Bum Lee, David L Mack, Mark Bothwell, Claire D Clelland, Deok-Ho Kim

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

Article in Biomaterials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 12% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

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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

10 authors at 4 institutions in 2 countries.

Changho ChunDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Alec S T SmithInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98109, USA; Department of Physiology & Biophysics, University of Washington, Seattle, WA, 98195, USA.
Hyejin KimDepartment of Chemical Engineering, University of Seoul, Seoul, South Korea.
Dana S KamenzDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Jung Hyun LeeInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98109, USA; Division of Dermatology, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
Jong Bum LeeDepartment of Chemical Engineering, University of Seoul, Seoul, South Korea.
David L MackDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98109, USA; Department of Rehabilitation Medicine, University of Washington, Seattle, WA, 98195, USA.
Mark BothwellInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98109, USA; Department of Physiology & Biophysics, University of Washington, Seattle, WA, 98195, USA.
Claire D ClellandGladstone Institute, San Francisco, CA, 94158, USA; Department of Neurology, University of California San Francisco, San Francisco, CA, 94143, USA.
Deok-Ho KimDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98109, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21205, USA; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA; Department of Physical Medicine and Rehabilitation, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. Electronic address: dhkim@jhu.edu.
University of Washington · USUniversity of Seoul · KRGladstone Institutes · USJohns Hopkins University · US

Funding

NCCIH Supplement to NCATS/CTSA Program for KL2 Scholars - M. SoddersKL2TR002317 · NCATS · UNIVERSITY OF WASHINGTON · PI Christy Michelle McKinney · 2017 to 2026
$14.5M
TISSUE ENGINEERED HUMAN NEUROMUSCULAR JUNCTIONS FOR MODELING AXONAL NEUROPATHYR01NS094388 · NINDS · UNIVERSITY OF WASHINGTON · PI KIM, DEOK-HO · 2017 to 2021
$1.7M
NCATS NIH HHS KL2 TR002317NINDS NIH HHS R01 NS094388
6 · The paper itself

Abstract

Neurons derived from human induced pluripotent stem cells (hiPSCs) are powerful tools for modeling neural pathophysiology and preclinical efficacy/toxicity screening of novel therapeutic compounds. However, human neurons cultured in vitro typically do not fully recapitulate the physiology of the human nervous system, especially in terms of exhibiting morphological maturation, longevity, and electrochemical signaling ability comparable to that of adult human neurons. In this study, we investigated the potential for astrocyte-derived extracellular vesicles (EVs) to modulate survival and electrophysiological function of human neurons in vitro. Specifically, we demonstrate that EVs obtained from human astrocytes promote enhanced single cell electrophysiological function and anti-apoptotic behavior in a homogeneous population of human iPSC-derived cortical neurons. Furthermore, EV-proteomic analysis was performed to identify cargo proteins with the potential to promote the physiological enhancement observed. EV cargos were found to include neuroprotective proteins such as heat shock proteins, alpha-synuclein, and lipoprotein receptor-related protein 1 (LRP1), as well as apolipoprotein E (APOE), which negatively regulates neuronal apoptosis, and a peroxidasin homolog that supports neuronal oxidative stress management. Proteins that positively regulate neuronal excitability and synaptic development were also detected, such as potassium channel tetramerization domain containing 12 (KCTD12), glucose-6- phosphate dehydrogenase (G6PD), kinesin family member 5B (KIF5B), spectrin-alpha non-erythrocytic1 (SPTAN1). The remarkable improvements in electrophysiological function and evident inhibition of apoptotic signaling in cultured neurons exposed to these cargos may hold significance for improving preclinical in vitro screening modalities. In addition, our collected data highlight the potential for EV-based therapeutics as a potential class of future clinical treatment for tackling inveterate central and peripheral neuropathies.

Indexed as

Extracellular VesiclesInduced Pluripotent Stem CellsPeripheral Nervous System DiseasesAstrocytesCells, CulturedHumansNeuronsProteomicsAstrocyteElectrophysiologyExtracellular vesiclesHuman cortical neuronSurvival

Identifiers

PMID33631652
PMCPMC8044026
OpenAlexW3126779750

What OpenQuestion holds

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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.