Evidence map›Paper›PMID 28717420›Full record

ArticleJournal of extracellular vesicles2017

Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells.

Xiaohua Zhu, Mohamed Badawi, Steven Pomeroy, Dhruvitkumar S Sutaria, Zhiliang Xie, Alice Baek, Jinmai Jiang, Ola A Elgamal, Xiaokui Mo, Krista La Perle and 3 more

Open access · goldAbstract read
In one paragraph

Article in Journal of extracellular vesicles, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 360 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
360citing papers in PubMed, 1 pooled it
10.9field-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

360 citing papers in PubMed, 1 synthesis or guideline pooled it, 564 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Isolation of Extracellular Vesicles From Mouse Brown Adipose Tissue Secretome Using Size-Exclusion Chromatography.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Toward an age of CRISPR delivery with non-viral biologics.Molecular therapy. Nucleic acids · 2026
    Article

300 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

13 authors at 2 institutions in 1 country.

Xiaohua ZhuCollege of Pharmacy, The Ohio State University, Columbus, OH, USA.
Mohamed BadawiCollege of Pharmacy, The Ohio State University, Columbus, OH, USA.
Steven PomeroyCollege of Pharmacy, University of Florida, Gainesville, FL, USA.
Dhruvitkumar S SutariaCollege of Pharmacy, The Ohio State University, Columbus, OH, USA.
Zhiliang XieCollege of Pharmacy, The Ohio State University, Columbus, OH, USA.
Alice BaekCollege of Pharmacy, The Ohio State University, Columbus, OH, USA.
Jinmai JiangCollege of Pharmacy, University of Florida, Gainesville, FL, USA.
Ola A ElgamalCollege of Pharmacy, The Ohio State University, Columbus, OH, USA.
Xiaokui MoDepartment of Biostatistics, The Ohio State University, Columbus, OH, USA.
Krista La PerleCollege of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Jeffrey ChalmersCollege of Engineering, The Ohio State University, Columbus, OH, USA.
Thomas D SchmittgenCollege of Pharmacy, University of Florida, Gainesville, FL, USA.
Mitch A PhelpsCollege of Pharmacy, The Ohio State University, Columbus, OH, USA.
The Ohio State University · USUniversity of Florida · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
Targeted delivery of microRNA-loaded microvesicle for cancer therapyUH3TR000914 · NCATS · UNIVERSITY OF FLORIDA · PI PHELPS, MITCH A, SCHMITTGEN, THOMAS D. · 2016 to 2017
$1.6M
Targeted delivery of microRNA-loaded microvesicle for cancer therapyUH2TR000914 · NCATS · UNIVERSITY OF FLORIDA · PI PHELPS, MITCH A, SCHMITTGEN, THOMAS D. · 2013 to 2015
$1.5M
NCATS NIH HHS UH2 TR000914NCATS NIH HHS UH3 TR000914NCI NIH HHS P30 CA016058
6 · The paper itself

Abstract

Extracellular vesicles (EVs) are under evaluation as therapeutics or as vehicles for drug delivery. Preclinical studies of EVs often use mice or other animal models to assess efficacy and disposition. However, as most EVs under evaluation are derived from human cells, they may elicit immune responses which may contribute to toxicities or enhanced EV clearance. Furthermore, EVs from different cell sources or EVs comprising various cargo may differ with respect to immunogenicity or toxicity. To assess EV-induced immune response and toxicity, we dosed C57BL/6 mice with EVs intravenously and intraperitoneally for 3 weeks. EVs were harvested from wild type or engineered HEK293T cells which were modified to produce EVs loaded with miR-199a-3p and chimeric proteins. Blood was collected to assess hematology, blood chemistry, and immune markers. Spleen cells were immunophenotyped, and tissues were harvested for gross necropsy and histopathological examination. No signs of toxicity were observed, and minimal evidence of changes in immune markers were noted in mice dosed with engineered, but not with wild type EVs. This study provides a framework for assessment of immunogenicity and toxicity that will be required as EVs from varying cell sources are tested within numerous animal models and eventually in humans.

Indexed as

C57BL/6cytokinesdrug carriersExosomesimmunogenicityimmunophenotypingmiR-199a-3ptoxicity

Identifiers

PMID28717420
PMCPMC5505007
OpenAlexW2621533948

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.