Sonoporation of Human Renal Proximal Tubular Epithelial Cells In Vitro to Enhance the Liberation of Intracellular miRNA Biomarkers.

Biomarkers Kidney disease Liquid biopsy Microbubbles Sonoporation Ultrasound insonation miRNA

Journal

Ultrasound in medicine & biology
ISSN: 1879-291X
Titre abrégé: Ultrasound Med Biol
Pays: England
ID NLM: 0410553

Informations de publication

Date de publication:
06 2022
Historique:
received: 22 09 2021
revised: 11 01 2022
accepted: 29 01 2022
pubmed: 22 3 2022
medline: 28 4 2022
entrez: 21 3 2022
Statut: ppublish

Résumé

Ultrasound has previously been demonstrated to non-invasively cause tissue disruption. Small animal studies have demonstrated that this effect can be enhanced by contrast microbubbles and has the potential to be clinically beneficial in techniques such as targeted drug delivery or enhancing liquid biopsies when a physical biopsy may be inappropriate. Cavitating microbubbles in close proximity to cells increases membrane permeability, allowing small intracellular molecules to leak into the extracellular space. This study sought to establish whether cavitating microbubbles could liberate cell-specific miRNAs, augmenting biomarker detection for non-invasive liquid biopsies. Insonating human polarized renal proximal tubular epithelial cells (RPTECs), in the presence of SonoVue microbubbles, revealed that cellular health could be maintained while achieving the release of miRNAs, miR-21, miR-30e, miR-192 and miR-194 (respectively, 10.9-fold, 7.17-fold, 5.95-fold and 5.36-fold). To examine the mechanism of release, RPTECs expressing enhanced green fluorescent protein were generated and the protein successfully liberated. Cell polarization, cellular phenotype and cell viability after sonoporation were measured by a number of techniques. Ultrastructural studies using electron microscopy showed gap-junction disruption and pore formation on cellular surfaces. These studies revealed that cell-specific miRNAs can be non-specifically liberated from RPTECs by sonoporation without a significant decrease in cell viability.

Identifiants

pubmed: 35307235
pii: S0301-5629(22)00041-2
doi: 10.1016/j.ultrasmedbio.2022.01.019
pii:
doi:

Substances chimiques

Biomarkers 0
MicroRNAs 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1019-1032

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R505638/1
Pays : United Kingdom

Informations de copyright

Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest This work was funded by a BBSRC:National Productivity Investment Fund PhD Scholarship co-funded by GSK (BB/R505638/1) awarded to J.H. and L.D. L.D. is supported by a Senior Kidney Research UK Fellowship (SF_001_20181122).

Auteurs

Oliver Teenan (O)

Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.

Vishal Sahni (V)

GlaxoSmithKline, Medical Research Centre, Stevenage, UK.

Robert B Henderson (RB)

GlaxoSmithKline, Medical Research Centre, Stevenage, UK.

Bryan R Conway (BR)

Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.

Carmel M Moran (CM)

Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.

Jeremy Hughes (J)

Centre for Inflammation Research, University of Edinburgh, Queens Medical Research Institute, Edinburgh, UK.

Laura Denby (L)

Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK. Electronic address: laura.denby@ed.ac.uk.

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Classifications MeSH