Evidence map›Paper›PMID 38908756›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2024

Auto-loaded TRAIL-exosomes derived from induced neural stem cells for brain cancer therapy.

Xiaopei Zhang, Hannah Taylor, Alain Valdivia, Rajaneekar Dasari, Andrew Buckley, Emily Bonacquisti, Juliane Nguyen, Krishna Kanchi, David L Corcoran, Laura E Herring and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Extracellular Vesicle-Based Drug Delivery Systems in Cancer Therapy.International journal of molecular sciences · 2025
    Review
  9. Review
  10. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Xiaopei ZhangEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hannah TaylorEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alain ValdiviaEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Rajaneekar DasariEshelman Institute for Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Andrew BuckleyEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Emily BonacquistiEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Juliane NguyenEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Krishna KanchiDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
David L CorcoranDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Laura E HerringMichael Hooker Proteomics Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Dennis A SteindlerEshelman Institute for Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Steindler Consulting, Boston, MA, USA.
Albert BaldwinLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Shawn HingtgenEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: hingtgen@email.unc.edu.
Andrew Benson SatterleeEshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman Institute for Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: satterle@email.unc.edu.

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
A consortium effort to translate therapies for neurological diseases via an ex vivo organotypic platformU01TR003715 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BALDWIN, ALBERT SIDNEY, FLORES, CATHERINE T · 2021 to 2024
$4.6M
Engineering stem cell therapies to understand and overcome glioblastoma adaptionR01NS099368 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HINGTGEN, SHAWN · 2017 to 2021
$1.6M
NCATS NIH HHS U01 TR003715NCI NIH HHS P30 CA016086NINDS NIH HHS R01 NS099368
6 · The paper itself

Abstract

Transdifferentiation (TD), a somatic cell reprogramming process that eliminates pluripotent intermediates, creates cells that are ideal for personalized anti-cancer therapy. Here, we provide the first evidence that extracellular vesicles (EVs) from TD-derived induced neural stem cells (Exo-iNSCs) are an efficacious treatment strategy for brain cancer. We found that genetically engineered iNSCs generated EVs loaded with the tumoricidal gene product TRAIL at nearly twice the rate of their parental fibroblasts, and TRAIL produced by iNSCs was naturally loaded into the lumen of EVs and arrayed across their outer membrane (Exo-iNSC-TRAIL). Uptake studies in ex vivo organotypic brain slice cultures showed that Exo-iNSC-TRAIL selectively accumulates within tumor foci, and co-culture assays demonstrated that Exo-iNSC-TRAIL killed metastatic and primary brain cancer cells more effectively than free TRAIL. In an orthotopic mouse model of brain cancer, Exo-iNSC-TRAIL reduced breast-to-brain tumor xenografts by approximately 3000-fold compared to treatment with free TRAIL, with all Exo-iNSC-TRAIL treated animals surviving through 90 days post-treatment. In additional in vivo testing against aggressive U87 and invasive GBM8 glioblastoma tumors, Exo-iNSC-TRAIL also induced a statistically significant increase in survival. These studies establish a novel, easily generated, stable, tumor-targeted EV to efficaciously treat multiple forms of brain cancer.

Indexed as

Brain NeoplasmsExosomesNeural Stem CellsTNF-Related Apoptosis-Inducing LigandAnimalsCell Line, TumorFemaleHumansMiceMice, NudeTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanBrain cancerExosomesExtracellular vesiclesiNSCsTRAIL

Identifiers

PMID38908756
PMCPMC11283351

What Socratic 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 Socratic graph.