2020 Fiscal Year Annual Research Report
Dynamic monitoring of microvessel models in time and space
| Project/Area Number |
20F20806
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| Research Institution | The University of Tokyo |
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| Host Researcher |
松永 行子 (津田行子) 東京大学, 生産技術研究所, 准教授 (00533663)
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| Foreign Research Fellow |
CACHEUX JEAN 東京大学, 生産技術研究所, 外国人特別研究員
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| Project Period (FY) |
2020-11-13 – 2023-03-31
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| Keywords | microvessel / permeability / collgen gel / microfluidics |
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| Outline of Annual Research Achievements |
Firstly, we have built 3D-printed mechanical devices that interface the MV (microvessel) for fluidic handling and which are compatible with optical microscopy. Two distinct experiments have been setup to probe the vessel permeability properties: i) an hydrostatic set-up for macromolecular fluorescence based permeability analysis and ii) a pressure-driven vessel deformation characterization.
Microfabrication of MV with different type of cellular models (HUVECs, HUVECs treated with inhibitor and co-culture of HUVECs with Human pericytes) has been also realized and changes in permeability and mechanical reponse is currently being measured.
Moreover, we also have developed a 2D finite element model on COMSOL to simulate the poroelastic mechanical response of a microvessel embedded into a collagen matrix under a pressure stress. Preliminary results seems to show a dependence between the vessel permeability and its mechanical response, which is in accordance with experimental results.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Main objectives for the Nov 2020 – March 2021 period have been achieved.
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| Strategy for Future Research Activity |
The engineered microvessel (MV) model can now be observed and stimulated by pressure. We aim thereafter to characterize finely the MV properties while responding to chemicals and mechanical stresses.
To do so, and in addition to the macromolecular tracer assay and deformation analysis, pressure diffusion through the collagen matrix is going to be investigated. Moreover, a characterization of cells junctions will be realized. This package will allow us to test how the structure of the MV is associated to its permeability properties.
Then, a new 3D-printed device allowing cells and DNA release collection will be built. Thus, analysis of the DNA content will complete the validation of the MV model to test whether and how the barrier function alteration can be associated to molecular signal changes.
Finally, and once our model will be well characterized, we aim to investigate the controversial mechanism of tumor-associated enhanced permeability and retention effect (EPR effect) by observing changes in permeability as a consequence of a co-culturing cancer spheroids. In addition, transport and biodistribution of nano-objects is going to be measured to test whether a passive specific targeting of tumour area can occur into an in vitro tumour on chip. Active transport of nano-objects through the endothelial cell layer will also be studied.
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