Evidence map›Paper›PMID 33389284›Full record

ArticleAAPS PharmSciTech2021

Extracellular Vesicles Derived from a Human Brain Endothelial Cell Line Increase Cellular ATP Levels.

Kandarp M Dave, Wanzhu Zhao, Catherine Hoover, Anisha D'Souza, Devika S Manickam

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in AAPS PharmSciTech, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.4field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 66 citations in OpenAlex.

  1. Sequential-RSC pharmaceutics · 2026
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  11. Mitochondria-containing extracellular vesicles from mouse vs. human brain endothelial cells for ischemic stroke therapy.Journal of controlled release : official journal of the Controlled Release Society · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Kandarp M Dave *Graduate School of Pharmaceutical Sciences, Duquesne University, 453 Mellon Hall, 600 Forbes Avenue, Pittsburgh, Pennsylvania, 15282, USA.
Wanzhu Zhao *Graduate School of Pharmaceutical Sciences, Duquesne University, 453 Mellon Hall, 600 Forbes Avenue, Pittsburgh, Pennsylvania, 15282, USA.
Catherine HooverDepartment of Chemistry and Physics, Mansfield University, Mansfield, Pennsylvania, USA.
Anisha D'SouzaGraduate School of Pharmaceutical Sciences, Duquesne University, 453 Mellon Hall, 600 Forbes Avenue, Pittsburgh, Pennsylvania, 15282, USA.
Devika S ManickamGraduate School of Pharmaceutical Sciences, Duquesne University, 453 Mellon Hall, 600 Forbes Avenue, Pittsburgh, Pennsylvania, 15282, USA. soundaramanickd@duq.edu.ORCID http://orcid.org/0000-0002-6363-3679
Duquesne University · USMansfield University · US

Funding

Pain and Neurodegenerative Undergraduate Research Experiences: Interacting with community partners to build specialized and enhanced neurologic disease programs for undergraduates.R25NS100118 · NINDS · DUQUESNE UNIVERSITY · PI MICHAEL CASCIO, David Bruce Heisler · 2018 to 2026
$825k
NINDS NIH HHS R25 NS100118
6 · The paper itself

Abstract

Engineered cell-derived extracellular vesicles (EVs) such as exosomes and microvesicles hold immense potential as safe and efficient drug carriers due to their lower immunogenicity and inherent homing capabilities to target cells. In addition to innate vesicular cargo such as lipids, proteins, and nucleic acids, EVs are also known to contain functional mitochondria/mitochondrial DNA that can be transferred to recipient cells to increase cellular bioenergetics. In this proof-of-concept study, we isolated naïve EVs and engineered EVs loaded with an exogenous plasmid DNA encoding for brain-derived neurotrophic factor (BDNF-EVs) from hCMEC/D3, a human brain endothelial cell line, and RAW 264.7 macrophages. We tested whether mitochondrial components in naïve or engineered EVs can increase ATP levels in the recipient brain endothelial cells. EVs (e.g., exosomes and microvesicles; EXOs and MVs) were isolated from the conditioned medium of either untreated (naïve) or pDNA-transfected (Luc-DNA or BDNF-DNA) cells using a differential centrifugation method. RAW 264.7 cell line-derived EVs showed a significantly higher DNA loading and increased luciferase expression in the recipient hCMEC/D3 cells at 72 h compared with hCMEC/D3 cell line-derived EVs. Naïve EVs from hCMEC/D3 cells and BDNF-EVs from RAW 264.7 cells showed a small, but a significantly greater increase in the ATP levels of recipient hCMEC/D3 cells at 24 and 48 h post-exposure. In summary, we have demonstrated (1) differences in exogenous pDNA loading into EVs as a function of cell type using brain endothelial and macrophage cell lines and (2) EV-mediated increases in the intracellular ATP levels in the recipient hCMEC/D3 monolayers.

Indexed as

Adenosine TriphosphateAnimalsBrainCell LineDNA, MitochondrialDrug CarriersEndothelial CellsEnergy MetabolismExtracellular VesiclesHumansMiceProof of Concept StudyRAW 264.7 CellsAdenosine TriphosphateDNA, MitochondrialDrug CarriersATP increasebrain endothelial cellsexosomes and microvesiclesischemic strokemitochondria and mtDNA

Identifiers

PMID33389284
PMCPMC8451174
OpenAlexW3118997739

What OpenQuestion holds

Textmetadata
LicenceTDM
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.