Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening

Abstract Patient-derived cellular models become an increasingly powerful tool to model human diseases for precision medicine approaches. The identification of robust cellular disease phenotypes in these models paved the way towards high throughput screenings (HTS) including the implementation of lab...

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Autores principales: Ibrahim Boussaad, Gérald Cruciani, Silvia Bolognin, Paul Antony, Claire M. Dording, Yong-Jun Kwon, Peter Heutink, Eugenio Fava, Jens C. Schwamborn, Rejko Krüger
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/7839939082c44d75981d01067b8f8bf2
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spelling oai:doaj.org-article:7839939082c44d75981d01067b8f8bf22021-12-02T15:22:56ZIntegrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening10.1038/s41598-021-81129-32045-2322https://doaj.org/article/7839939082c44d75981d01067b8f8bf22021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81129-3https://doaj.org/toc/2045-2322Abstract Patient-derived cellular models become an increasingly powerful tool to model human diseases for precision medicine approaches. The identification of robust cellular disease phenotypes in these models paved the way towards high throughput screenings (HTS) including the implementation of laboratory advanced automation. However, maintenance and expansion of cells for HTS remains largely manual work. Here, we describe an integrated, complex automated platform for HTS in a translational research setting also designed for maintenance and expansion of different cell types. The comprehensive design allows automation of all cultivation steps and is flexible for development of methods for variable cell types. We demonstrate protocols for controlled cell seeding, splitting and expansion of human fibroblasts, induced pluripotent stem cells (iPSC), and neural progenitor cells (NPC) that allow for subsequent differentiation into different cell types and image-based multiparametric screening. Furthermore, we provide automated protocols for neuronal differentiation of NPC in 2D culture and 3D midbrain organoids for HTS. The flexibility of this multitask platform makes it an ideal solution for translational research settings involving experiments on different patient-derived cellular models for precision medicine.Ibrahim BoussaadGérald CrucianiSilvia BologninPaul AntonyClaire M. DordingYong-Jun KwonPeter HeutinkEugenio FavaJens C. SchwambornRejko KrügerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ibrahim Boussaad
Gérald Cruciani
Silvia Bolognin
Paul Antony
Claire M. Dording
Yong-Jun Kwon
Peter Heutink
Eugenio Fava
Jens C. Schwamborn
Rejko Krüger
Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening
description Abstract Patient-derived cellular models become an increasingly powerful tool to model human diseases for precision medicine approaches. The identification of robust cellular disease phenotypes in these models paved the way towards high throughput screenings (HTS) including the implementation of laboratory advanced automation. However, maintenance and expansion of cells for HTS remains largely manual work. Here, we describe an integrated, complex automated platform for HTS in a translational research setting also designed for maintenance and expansion of different cell types. The comprehensive design allows automation of all cultivation steps and is flexible for development of methods for variable cell types. We demonstrate protocols for controlled cell seeding, splitting and expansion of human fibroblasts, induced pluripotent stem cells (iPSC), and neural progenitor cells (NPC) that allow for subsequent differentiation into different cell types and image-based multiparametric screening. Furthermore, we provide automated protocols for neuronal differentiation of NPC in 2D culture and 3D midbrain organoids for HTS. The flexibility of this multitask platform makes it an ideal solution for translational research settings involving experiments on different patient-derived cellular models for precision medicine.
format article
author Ibrahim Boussaad
Gérald Cruciani
Silvia Bolognin
Paul Antony
Claire M. Dording
Yong-Jun Kwon
Peter Heutink
Eugenio Fava
Jens C. Schwamborn
Rejko Krüger
author_facet Ibrahim Boussaad
Gérald Cruciani
Silvia Bolognin
Paul Antony
Claire M. Dording
Yong-Jun Kwon
Peter Heutink
Eugenio Fava
Jens C. Schwamborn
Rejko Krüger
author_sort Ibrahim Boussaad
title Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening
title_short Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening
title_full Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening
title_fullStr Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening
title_full_unstemmed Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening
title_sort integrated, automated maintenance, expansion and differentiation of 2d and 3d patient-derived cellular models for high throughput drug screening
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/7839939082c44d75981d01067b8f8bf2
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