Use of dual-flow bioreactor to develop a simplified model of nervous-cardiovascular systems crosstalk: A preliminary assessment.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2020
Historique:
received: 22 07 2020
accepted: 05 11 2020
entrez: 30 11 2020
pubmed: 1 12 2020
medline: 5 1 2021
Statut: epublish

Résumé

Chronic conditions requiring long-term rehabilitation therapies, such as hypertension, stroke, or cancer, involve complex interactions between various systems/organs of the body and mutual influences, thus implicating a multiorgan approach. The dual-flow IVTech LiveBox2 bioreactor is a recently developed inter-connected dynamic cell culture model able to mimic organ crosstalk, since cells belonging to different organs can be connected and grown under flow conditions in a more physiological environment. This study aims to setup for the first time a 2-way connected culture of human neuroblastoma cells, SH-SY5Y, and Human Coronary Artery Smooth Muscle Cells, HCASMC through a dual-flow IVTech LiveBox2 bioreactor, in order to represent a simplified model of nervous-cardiovascular systems crosstalk, possibly relevant for the above-mentioned diseases. The system was tested by treating the cells with 10nM angiotensin II (AngII) inducing PKCβII/HuR/VEGF pathway activation, since AngII and PKCβII/HuR/VEGF pathway are relevant in cardiovascular and neuroscience research. Three different conditions were applied: 1- HCASMC and SH-SY5Y separately seeded in petri dishes (static condition); 2- the two cell lines separately seeded under flow (dynamic condition); 3- the two lines, seeded in dynamic conditions, connected, each maintaining its own medium, with a membrane as interface for biohumoral changes between the two mediums, and then treated. We detected that only in condition 3 there was a synergic AngII-dependent VEGF production in SH-SY5Y cells coupled to an AngII-dependent PKCβII/HuR/VEGF pathway activation in HCASMC, consistent with the observed physiological response in vivo. HCASMC response to AngII seems therefore to be generated by/derived from the reciprocal cell crosstalk under the dynamic inter-connection ensured by the dual flow LiveBox 2 bioreactor. This system can represent a useful tool for studying the crosstalk between organs, helpful for instance in rehabilitation research or when investigating chronic diseases; further, it offers the advantageous opportunity of cultivating each cell line in its own medium, thus mimicking, at least in part, distinct tissue milieu.

Identifiants

pubmed: 33253266
doi: 10.1371/journal.pone.0242627
pii: PONE-D-20-22750
pmc: PMC7703955
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0242627

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Nicoletta Marchesi (N)

Department of Drug Sciences, Pharmacology Section, University of Pavia, Pavia, Italy.

Annalisa Barbieri (A)

Department of Drug Sciences, Pharmacology Section, University of Pavia, Pavia, Italy.

Foroogh Fahmideh (F)

Department of Drug Sciences, Pharmacology Section, University of Pavia, Pavia, Italy.

Stefano Govoni (S)

Department of Drug Sciences, Pharmacology Section, University of Pavia, Pavia, Italy.

Alice Ghidoni (A)

Center for Cardiac Arrhythmias of Genetic Origin, Istituto Auxologico Italiano, IRCCS, Milan, Italy.

Gianfranco Parati (G)

Department of Cardiovascular, Neural and Metabolic Sciences, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.

Emilio Vanoli (E)

Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Cardiovascular Department, IRCCS Multimedica, Sesto San Giovanni, Italy.

Alessia Pascale (A)

Department of Drug Sciences, Pharmacology Section, University of Pavia, Pavia, Italy.

Laura Calvillo (L)

Department of Cardiovascular, Neural and Metabolic Sciences, IRCCS Istituto Auxologico Italiano, Milan, Italy.

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