Evidence map›Paper›PMID 32467728›Full record

ArticleJournal of biological engineering2020

High-throughput screening of clinically approved drugs that prime nonviral gene delivery to human Mesenchymal stem cells.

Tyler Kozisek, Andrew Hamann, Albert Nguyen, Michael Miller, Sarah Plautz, Angela K Pannier

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

Article in Journal of biological engineering, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

7 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
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

6 authors at 2 institutions in 1 country.

Tyler Kozisek1Department of Biological Systems Engineering, University of Nebraska-Lincoln, 231 L.W. Chase Hall, Lincoln, NE USA.
Andrew Hamann1Department of Biological Systems Engineering, University of Nebraska-Lincoln, 231 L.W. Chase Hall, Lincoln, NE USA.
Albert Nguyen1Department of Biological Systems Engineering, University of Nebraska-Lincoln, 231 L.W. Chase Hall, Lincoln, NE USA.
Michael Miller2Department of Biomedical Engineering, Pennsylvania State University, 122 Chemical and Biomedical Engineering Building, University Park, PA USA.
Sarah Plautz1Department of Biological Systems Engineering, University of Nebraska-Lincoln, 231 L.W. Chase Hall, Lincoln, NE USA.
Angela K Pannier1Department of Biological Systems Engineering, University of Nebraska-Lincoln, 231 L.W. Chase Hall, Lincoln, NE USA.ORCID 0000-0002-7589-9351
University of Nebraska–Lincoln · USPennsylvania State University · US

Funding

UNMC Structural Biology CoreP20GM103427 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PAUL L SORGEN · 2012 to 2026
$59.2M
Using Cell Priming and Telecommunications Modeling to Enhance Gene Delivery for Stem Cell TherapiesDP2EB025760 · NIBIB · UNIVERSITY OF NEBRASKA LINCOLN · PI PANNIER, ANGELA K · 2017 to 2022
$2.8M
NIBIB NIH HHS DP2 EB025760NIGMS NIH HHS P20 GM103427
6 · The paper itself

Abstract

backgroundHuman mesenchymal stem cells (hMSCs) are intensely researched for applications in cell therapeutics due to their unique properties, however, intrinsic therapeutic properties of hMSCs could be enhanced by genetic modification. Viral transduction is efficient, but suffers from safety issues. Conversely, nonviral gene delivery, while safer compared to viral, suffers from inefficiency and cytotoxicity, especially in hMSCs. To address the shortcomings of nonviral gene delivery to hMSCs, our lab has previously demonstrated that pharmacological 'priming' of hMSCs with the glucocorticoid dexamethasone can significantly increase transfection in hMSCs by modulating transfection-induced cytotoxicity. This work seeks to establish a library of transfection priming compounds for hMSCs by screening 707 FDA-approved drugs, belonging to diverse drug classes, from the NIH Clinical Collection at four concentrations for their ability to modulate nonviral gene delivery to adipose-derived hMSCs from two human donors.

resultsMicroscope images of cells transfected with a fluorescent transgene were analyzed in order to identify compounds that significantly affected hMSC transfection without significant toxicity. Compound classes that increased transfection across both donors included glucocorticoids, antibiotics, and antihypertensives. Notably, clobetasol propionate, a glucocorticoid, increased transgene production 18-fold over unprimed transfection. Furthermore, compound classes that decreased transfection across both donors included flavonoids, antibiotics, and antihypertensives, with the flavonoid epigallocatechin gallate decreasing transgene production - 41-fold compared to unprimed transfection.

conclusionsOur screen of the NCC is the first high-throughput and drug-repurposing approach to identify nonviral gene delivery priming compounds in two donors of hMSCs. Priming compounds and classes identified in this screen suggest that modulation of proliferation, mitochondrial function, and apoptosis is vital for enhancing nonviral gene delivery to hMSCs.

Indexed as

AntibioticsAntihypertensiveGlucocorticoidHigh-throughput screenHuman mesenchymal stem cellsLipid-mediatedLipoplexesNIH clinical collectionNonviral gene deliveryPriming transfection

Identifiers

PMID32467728
PMCPMC7238544
OpenAlexW3029419122

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.