Evidence map›Paper›PMID 27240162›Full record

ArticleBiomaterials2016

Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival.

Antonella Mangraviti, Stephany Y Tzeng, David Gullotti, Kristen L Kozielski, Jennifer E Kim, Michael Seng, Sara Abbadi, Paula Schiapparelli, Rachel Sarabia-Estrada, Angelo Vescovi and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

66 citing papers in PubMed, 131 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Mesenchymal Stem Cells in Cancer Therapy.Advances in experimental medicine and biology · 2025
    Review
  6. Regenerative Glycopeptide Scaffolds Enhance BMP-4 Activity To Treat Pediatric Glioma.Regenerative engineering and translational medicine · 2025
    Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Nonviral nanoparticle gene delivery into the CNS for neurological disorders and brain cancer applications.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2023
    Review
  20. Nucleic acid drug vectors for diagnosis and treatment of brain diseases.Signal transduction and targeted therapy · 2023
    Review

6 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

15 authors at 2 institutions in 2 countries.

Antonella MangravitiDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Stephany Y TzengDepartment of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
David GullottiDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kristen L KozielskiDepartment of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Jennifer E KimDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael SengDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sara AbbadiDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Paula SchiapparelliDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rachel Sarabia-EstradaDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Angelo VescoviIRCSS Casa Sollievo della Sofferenza, Opera di San Pio da Pietrelcina, viale dei Cappuccini, 1, 71013 S. Giovanni Rotondo, Italy.
Henry BremDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alessandro OliviDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Betty TylerDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: btyler@jhmi.edu.
Jordan J GreenDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: green@jhu.edu.
Alfredo Quinones-HinojosaDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: aquinon2@jhmi.edu.
Johns Hopkins University · USCasa Sollievo della Sofferenza · IT

Funding

T32: Predoctoral and Postdoctoral Training Program in Nanotechnology for Cancer ResearchT32CA153952 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz · 2015 to 2026
$3.5M
Gene Delivery Nanoparticles to Treat GlioblastomaR01EB016721 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2013 to 2017
$1.9M
Nanoparticle Modified Human Fat Derived Mesenchymal Stem Cells for Brain Cancer (Change of Organization Application)R01CA195503 · NCI · MAYO CLINIC JACKSONVILLE · PI GREEN, JORDAN, QUINONES-HINOJOSA, ALFREDO · 2016 to 2020
$1.9M
BMP4 Engineered Mesenchymal Stem Cell Therapy for GlioblastomaR01CA183827 · NCI · MAYO CLINIC JACKSONVILLE · PI QUINONES-HINOJOSA, ALFREDO · 2015 to 2019
$1.9M
The Johns Hopkins Cancer Nanotechnology Training CenterR25CA153952 · NCI · JOHNS HOPKINS UNIVERSITY · PI MAO, HAI-QUAN, WIRTZ, DENIS · 2010 to 2014
$1.7M
Nanoparticles for selective and combinatorial delivery of siRNA to brain cancerF31CA196163 · NCI · JOHNS HOPKINS UNIVERSITY · PI KOZIELSKI, KRISTEN LYNN · 2015 to 2016
$68k
NCI NIH HHS F31 CA196163NCI NIH HHS R01 CA183827NCI NIH HHS R01 CA195503NCI NIH HHS R25 CA153952NCI NIH HHS T32 CA153952NIBIB NIH HHS R01 EB016721
6 · The paper itself

Abstract

There is a need for enabling non-viral nanobiotechnology to allow safe and effective gene therapy and cell therapy, which can be utilized to treat devastating diseases such as brain cancer. Human adipose-derived mesenchymal stem cells (hAMSCs) display high anti-glioma tropism and represent a promising delivery vehicle for targeted brain tumor therapy. In this study, we demonstrate that non-viral, biodegradable polymeric nanoparticles (NPs) can be used to engineer hAMSCs with higher efficacy (75% of cells) than leading commercially available reagents and high cell viability. To accomplish this, we engineered a poly(beta-amino ester) (PBAE) polymer structure to transfect hAMSCs with significantly higher efficacy than Lipofectamine™ 2000. We then assessed the ability of NP-engineered hAMSCs to deliver bone morphogenetic protein 4 (BMP4), which has been shown to have a novel therapeutic effect by targeting human brain tumor initiating cells (BTIC), a source of cancer recurrence, in a human primary malignant glioma model. We demonstrated that hAMSCs genetically engineered with polymeric nanoparticles containing BMP4 plasmid DNA (BMP4/NP-hAMSCs) secrete BMP4 growth factor while maintaining their multipotency and preserving their migration and invasion capacities. We also showed that this approach can overcome a central challenge for brain therapeutics, overcoming the blood brain barrier, by demonstrating that NP-engineered hAMSCs can migrate to the brain and penetrate the brain tumor after both intranasal and systemic intravenous administration. Critically, athymic rats bearing human primary BTIC-derived tumors and treated intranasally with BMP4/NP-hAMSCs showed significantly improved survival compared to those treated with control GFP/NP-hAMCSs. This study demonstrates that synthetic polymeric nanoparticles are a safe and effective approach for stem cell-based cancer-targeting therapies.

Indexed as

Genetic EngineeringMesenchymal Stem Cell TransplantationTransfectionAdipose TissueAnimalsBone Morphogenetic Protein 4Brain NeoplasmsCell LineCell Line, TumorDNAFemaleHumansMesenchymal Stem CellsNanoparticlesPolymersRatsBMP4 protein, humanBone Morphogenetic Protein 4DNApoly(beta-amino ester)PolymersAdipose-derived stem cellsBrain cancerGene deliveryNanoparticlesTumor stem cells

Identifiers

PMID27240162
PMCPMC4902753
OpenAlexW2408571709

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.