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Research Article
Bruno le Pioufle
Université Paris Saclay, ENS Paris Saclay, CNRS LUMIN, F91190 Gif-sur-Yvette
Corresponding Author
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The development of livers-on-a-chip aims to provide pharmaceutical companies with reliable systems to perform drug screening and toxicological studies. To that end, microfluidic systems are engineered to mimic the functions and architecture of this organ. In this context we have designed a device that reproduces series of liver microarchitectures, each permitting the 3D culture of hepatocytes by confining them to a chamber that is separated from the medium conveying channel by very thin slits. We modified the structure to ensure its compatibility with the culture of hepatocytes from different sources. Our device was adapted to the migratory and adhesion properties of HepaRG cells at various stages of differentiation. To prevent hepatoblast-like cells from migrating out of the chambers, the slit height was decreased and the medium flow rate increased. Maintaining already differentiated and less adherent cells within the chambers required desensitisation of the system to pressure variations. Using this device, it was possible to keep the cells alive for more than 14 days, during which they achieved a 3D organisation and acquired or maintained their differentiation into hepatocytes. With its multiple micro-chambers for hepatocyte culture, this microfluidic device architecture offers a promising opportunity to provide new tools for drug screening applications.
Keywords
3D, cells, HepaRG, 2D
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CURRENT STATUS: Published
View the published article at Scientific Reports.
Version 1
Posted 08 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 08 Feb, 2021
Reviews received
Received 23 Jan, 2021
Reviewers agreed
On 08 Jan, 2021
Reviewers invited
Invitations sent on 08 Jan, 2021
Editor assigned
On 08 Jan, 2021
Editor invited
On 06 Jan, 2021
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On 06 Jan, 2021
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On 30 Dec, 2020
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See the published version of this preprint at Scientific Reports.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Bruno le Pioufle
Université Paris Saclay, ENS Paris Saclay, CNRS LUMIN, F91190 Gif-sur-Yvette
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Scientific Reports.
Version 1
Posted 08 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 08 Feb, 2021
Reviews received
Received 23 Jan, 2021
Reviewers agreed
On 08 Jan, 2021
Reviewers invited
Invitations sent on 08 Jan, 2021
Editor assigned
On 08 Jan, 2021
Editor invited
On 06 Jan, 2021
Submission checks complete
On 06 Jan, 2021
First submitted
On 30 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Scientific Reports.
The development of livers-on-a-chip aims to provide pharmaceutical companies with reliable systems to perform drug screening and toxicological studies. To that end, microfluidic systems are engineered to mimic the functions and architecture of this organ. In this context we have designed a device that reproduces series of liver microarchitectures, each permitting the 3D culture of hepatocytes by confining them to a chamber that is separated from the medium conveying channel by very thin slits. We modified the structure to ensure its compatibility with the culture of hepatocytes from different sources. Our device was adapted to the migratory and adhesion properties of HepaRG cells at various stages of differentiation. To prevent hepatoblast-like cells from migrating out of the chambers, the slit height was decreased and the medium flow rate increased. Maintaining already differentiated and less adherent cells within the chambers required desensitisation of the system to pressure variations. Using this device, it was possible to keep the cells alive for more than 14 days, during which they achieved a 3D organisation and acquired or maintained their differentiation into hepatocytes. With its multiple micro-chambers for hepatocyte culture, this microfluidic device architecture offers a promising opportunity to provide new tools for drug screening applications.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This preprint is available for download as a PDF.
This is a list of supplementary files associated with this preprint. Click to download.
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