Bacterial extracellular vesicles indirectly destabilize a human stem cell-derived blood-brain barrier on-chip through pro-inflammatory stimulation of immune cells.

Overview

Authors: Louis P Widom¹, Panteha Torabian¹, Michelle A Trempel², Molly C McCloskey², Lea V Michel³, James L McGrath², Thomas R Gaborski¹

ORCID iDs: Louis P Widom, Panteha Torabian, Michelle A Trempel, Molly C McCloskey, Lea V Michel, James L McGrath, Thomas R Gaborski

Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, New York, USA
Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
School of Chemistry and Materials Science, Rochester Institute of Technology, Rochester, New York, USA

Institutions: Rochester Institute of Technology (United States); University of Rochester (United States)

Journal: Lab on a chip, volume 26, issue 11, pages 3327-3344

Dates: received 22 January 2026; accepted 6 April 2026; published online 7 April 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1039/d6lc00067c · PMID 41978430 · PMCID PMC13077281 · OpenAlex W7151250063

Open access: hybrid, a free copy (OpenAlex)

Status: data only

Categories: human (organism), cellular / molecular (subfield)

Methods: Spectral & time-frequency, Statistics

MeSH: Blood-Brain Barrier*, Escherichia coli*, Extracellular Vesicles*, Induced Pluripotent Stem Cells*, Lab-On-A-Chip Devices*, Cytokines, Endothelial Cells, Humans, Lipopolysaccharides, Macrophages, Microphysiological Systems, Pericytes, THP-1 Cells (* major topic)

Topic: Bacterial Infections and Vaccines (Microbiology, Immunology and Microbiology), according to OpenAlex

Funding: National Institute of Allergy and Infectious Diseases (R21AI163782); National Heart, Lung, and Blood Institute (R33HL154249); NIAID NIH HHS (R21 AI163782); NHLBI NIH HHS (R33 HL154249); NIA NIH HHS (U2C AG088071); National Institute on Aging (U2CAG088071); NIGMS NIH HHS (R35 GM153461); National Institute of General Medical Sciences (R35GM153461)

Citations: cited by 1 paper (Europe PMC); 95 references in the paper

Abstract

Pathogenic bacterial extracellular vesicles (BEVs) can disrupt the blood–brain barrier (BBB), leading to neuroinflammation. Prior in vitro studies of this process were performed in simple models that may have lacked important physiological factors. We sought to determine if treatment with Escherichia coli-derived BEVs could directly compromise the integrity of a BBB lab-on-chip model or if an immune component was required. Our device featured isogenic human induced pluripotent stem cell-derived brain microvascular endothelial-like cells (BMECs) and pericytes separated by an ultrathin, porous silicon nitride membrane. BEVs and free lipopolysaccharide (LPS) were capable of causing upregulation of intercellular adhesion molecule-1 on the BMEC surfaces, which is important for immune cell recruitment. However, neither BEVs nor LPS at physiologically-relevant doses caused pronounced loss of BMEC tight junction proteins, nor did they increase barrier permeability to small dye molecules. In contrast, stimulating THP-1 macrophages with BEVs led to increased production of pro-inflammatory cytokines, and conditioned media from the stimulated macrophages disrupted BMEC tight junctions and increased barrier permeability. Our work demonstrates the importance of incorporating an immune component in studies of BEV-mediated disruption of BBB models.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

Datasets cited

figshare:31118659, at figshare; found in “Data availability”

Data availability

The majority of relevant data for this study are presented in the manuscript and supplementary information (SI). Fluorescence data, NTA data, western blot data, LPS quantification data, permeability data, and cytokine concentration data are available on Figshare (https://doi.org/10.6084/m9.figshare.31118659).

Supplementary information is available. See DOI: https://doi.org/10.1039/d6lc00067c.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 2, 28 September 2026

Publisher: n/a → Royal Society of Chemistry

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 13 MeSH terms, 8 funders, 93 references.

Cite

This paper

Widom, L. P., Torabian, P., Trempel, M. A., McCloskey, M. C., Michel, L. V., McGrath, J. L., & Gaborski, T. R. (2026). Bacterial extracellular vesicles indirectly destabilize a human stem cell-derived blood-brain barrier on-chip through pro-inflammatory stimulation of immune cells. Lab on a chip, 26(11), 3327-3344. https://doi.org/10.1039/d6lc00067c

BibTeX

@article{widom2026bacterial, author = {Widom, Louis P and Torabian, Panteha and Trempel, Michelle A and McCloskey, Molly C and Michel, Lea V and McGrath, James L and Gaborski, Thomas R}, title = {{Bacterial extracellular vesicles indirectly destabilize a human stem cell-derived blood-brain barrier on-chip through pro-inflammatory stimulation of immune cells}}, journal = {Lab on a chip}, year = {2026}, month = jun, volume = {26}, number = {11}, pages = {3327--3344}, publisher = {Royal Society of Chemistry}, issn = {1473-0197}, doi = {10.1039/d6lc00067c}, url = {https://doi.org/10.1039/d6lc00067c}, pmid = {41978430}, pmcid = {PMC13077281} }

RIS

TY - JOUR AU - Widom, Louis P AU - Torabian, Panteha AU - Trempel, Michelle A AU - McCloskey, Molly C AU - Michel, Lea V AU - McGrath, James L AU - Gaborski, Thomas R TI - Bacterial extracellular vesicles indirectly destabilize a human stem cell-derived blood-brain barrier on-chip through pro-inflammatory stimulation of immune cells T2 - Lab on a chip J2 - Lab Chip PY - 2026 DA - 2026/06/02 VL - 26 IS - 11 SP - 3327 EP - 3344 SN - 1473-0197 PB - Royal Society of Chemistry DO - 10.1039/d6lc00067c UR - https://doi.org/10.1039/d6lc00067c LA - en ER -

CSL-JSON

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