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A human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles

Mesenchymal stromal cell (MSC)‐derived small extracellular vesicles (sEVs) show therapeutic potential in multiple disease models, including kidney injury. Clinical translation of sEVs requires further preclinical and regulatory developments, including elucidation of the biodistribution and mode of a...

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Autores principales: Nguyen, Vivian V. T., Ye, Shicheng, Gkouzioti, Vasiliki, van Wolferen, Monique E., Yengej, Fjodor Yousef, Melkert, Dennis, Siti, Sofia, de Jong, Bart, Besseling, Paul J., Spee, Bart, van der Laan, Luc J. W., Horland, Reyk, Verhaar, Marianne C., van Balkom, Bas W. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667402/
https://www.ncbi.nlm.nih.gov/pubmed/36382606
http://dx.doi.org/10.1002/jev2.12280
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author Nguyen, Vivian V. T.
Ye, Shicheng
Gkouzioti, Vasiliki
van Wolferen, Monique E.
Yengej, Fjodor Yousef
Melkert, Dennis
Siti, Sofia
de Jong, Bart
Besseling, Paul J.
Spee, Bart
van der Laan, Luc J. W.
Horland, Reyk
Verhaar, Marianne C.
van Balkom, Bas W. M.
author_facet Nguyen, Vivian V. T.
Ye, Shicheng
Gkouzioti, Vasiliki
van Wolferen, Monique E.
Yengej, Fjodor Yousef
Melkert, Dennis
Siti, Sofia
de Jong, Bart
Besseling, Paul J.
Spee, Bart
van der Laan, Luc J. W.
Horland, Reyk
Verhaar, Marianne C.
van Balkom, Bas W. M.
author_sort Nguyen, Vivian V. T.
collection PubMed
description Mesenchymal stromal cell (MSC)‐derived small extracellular vesicles (sEVs) show therapeutic potential in multiple disease models, including kidney injury. Clinical translation of sEVs requires further preclinical and regulatory developments, including elucidation of the biodistribution and mode of action (MoA). Biodistribution can be determined using labelled sEVs in animal models which come with ethical concerns, are time‐consuming and expensive, and may not well represent human physiology. We hypothesised that, based on developments in microfluidics and human organoid technology, in vitro multi‐organ‐on‐a‐chip (MOC) models allow us to study effects of sEVs in modelled human organs like kidney and liver in a semi‐systemic manner. Human kidney‐ and liver organoids combined by microfluidic channels maintained physiological functions, and a kidney injury model was established using hydrogenperoxide. MSC‐sEVs were isolated, and their size, density and potential contamination were analysed. These sEVs stimulated recovery of the renal epithelium after injury. Microscopic analysis shows increased accumulation of PKH67‐labelled sEVs not only in injured kidney cells, but also in the unharmed liver organoids, compared to healthy control conditions. In conclusion, this new MOC model recapitulates therapeutic efficacy and biodistribution of MSC‐sEVs as observed in animal models. Its human background allows for in‐depth analysis of the MoA and identification of potential side effects.
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spelling pubmed-96674022022-11-17 A human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles Nguyen, Vivian V. T. Ye, Shicheng Gkouzioti, Vasiliki van Wolferen, Monique E. Yengej, Fjodor Yousef Melkert, Dennis Siti, Sofia de Jong, Bart Besseling, Paul J. Spee, Bart van der Laan, Luc J. W. Horland, Reyk Verhaar, Marianne C. van Balkom, Bas W. M. J Extracell Vesicles Research Articles Mesenchymal stromal cell (MSC)‐derived small extracellular vesicles (sEVs) show therapeutic potential in multiple disease models, including kidney injury. Clinical translation of sEVs requires further preclinical and regulatory developments, including elucidation of the biodistribution and mode of action (MoA). Biodistribution can be determined using labelled sEVs in animal models which come with ethical concerns, are time‐consuming and expensive, and may not well represent human physiology. We hypothesised that, based on developments in microfluidics and human organoid technology, in vitro multi‐organ‐on‐a‐chip (MOC) models allow us to study effects of sEVs in modelled human organs like kidney and liver in a semi‐systemic manner. Human kidney‐ and liver organoids combined by microfluidic channels maintained physiological functions, and a kidney injury model was established using hydrogenperoxide. MSC‐sEVs were isolated, and their size, density and potential contamination were analysed. These sEVs stimulated recovery of the renal epithelium after injury. Microscopic analysis shows increased accumulation of PKH67‐labelled sEVs not only in injured kidney cells, but also in the unharmed liver organoids, compared to healthy control conditions. In conclusion, this new MOC model recapitulates therapeutic efficacy and biodistribution of MSC‐sEVs as observed in animal models. Its human background allows for in‐depth analysis of the MoA and identification of potential side effects. John Wiley and Sons Inc. 2022-11-16 2022-11 /pmc/articles/PMC9667402/ /pubmed/36382606 http://dx.doi.org/10.1002/jev2.12280 Text en © 2022 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Nguyen, Vivian V. T.
Ye, Shicheng
Gkouzioti, Vasiliki
van Wolferen, Monique E.
Yengej, Fjodor Yousef
Melkert, Dennis
Siti, Sofia
de Jong, Bart
Besseling, Paul J.
Spee, Bart
van der Laan, Luc J. W.
Horland, Reyk
Verhaar, Marianne C.
van Balkom, Bas W. M.
A human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles
title A human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles
title_full A human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles
title_fullStr A human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles
title_full_unstemmed A human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles
title_short A human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles
title_sort human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667402/
https://www.ncbi.nlm.nih.gov/pubmed/36382606
http://dx.doi.org/10.1002/jev2.12280
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