Directing cell differentiation in organ-on-chip devices through microarchitecture and supported lipid bilayers

Nicole Jeane Louise Zeijen

Research output: ThesisPhD Thesis - Research UT, graduation UT

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Abstract

Stem cells react to their environment to develop into the final cell type. Identifying the physical and chemical cues which regulate this cell differentiation in tissues in vivo is very valuable the construction of in vitro models. The three-dimensional models are a better mimic of the in vivo microenvironment, so we constructed a microenvironment which contains both a microarchitecture to create a three-dimensional cell network and is capable to deliver the chemical cues needed for cell differentiation. To accomplish this a polymer (PDMS) microfluidic device is made with a microarchitecture of pillars. These pillars provide human mesenchymal stem cells (hMSCs) with the three dimensional support to form a cellular network, while the hMSCs can survive for up to 3 weeks in the microfluidic device.

The chemical cues in an in vitro model are given by adding a coating with ligands designed for binding or to provide the cells with information for differentiation. In the different tissues in the body these ligands can move when pulled on in soft tissues (such as adipose tissue) or stay in place in harder tissues (such as bone). The movability of the binding ligands RGD is instrumental for the morphology of the hMSCs and can effectively “hide” the stiffness of the underlying substrate. This difference of morphology of hMSCs can help steer the differentiation towards adipose tissue or bone. By using a supported lipid bilayer (SLB) and vary between a mobile and an immobile SLB the movability of the RGD ligands is tuned.

Coating the pillars with the SLB combines physical and chemical cues. The hMSCs cultured in the device again formed the cellular network, adhered to the RGD in the SLB. Ligands to instruct differentiation to bone (TGF-β1) is added to the SLB to test its availability to cultured cells. TGF-β1 presence on the SLB is established and this brings the SLB one step closer to being a functional cell instructive coating.

The physical and chemical cues that can be obtained by using a microarchitecture in a microfluidic device combined with an SLB coating laden with adhering and instructive ligands are promising in the construction of in vitro models representative of in vivo tissues.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Twente
Supervisors/Advisors
  • Jonkheijm, P., Supervisor
  • van der Meer, A.D., Co-Supervisor
  • Bennink, Martin L., Co-Supervisor
Award date4 Jun 2021
Place of PublicationEnschede
Publisher
Print ISBNs978-90-365-5190-8
DOIs
Publication statusPublished - 4 Jun 2021

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