Neurodegenerative disorders are characterised by the activation of brain-resident microglia
cells and by the infiltration of peripheral T cells. However, their interplay
in disease has not been clarified yet. It is difficult to investigate complex cellular
dynamics in living animals, and simple two-dimensional (2D) cell culture models do
not resemble the soft 3D structure of brain tissue. Therefore, we developed a biomimetic
3D in vitro culture system for co-cultivation of microglia and T cells. As the
activation and/or migration of immune cells in the brain might be affected by components
of the extracellular matrix, defined 3D fibrillar collagen I-based matrices were
constructed and modified with hyaluronan and/or chondroitin sulphate, resembling
aspects of brain extracellular matrix. Murine microglia and spleen-derived T cells
were cultured alone or in co-culture on the constructed matrices. Microglia exhibited
in vivo-like morphology and T cells showed enhanced survival when co-cultured
with microglia or to a minor degree in the presence of glia-conditioned medium.
The open and porous fibrillar structure of the matrix allowed for cell invasion and
direct cell-cell interaction, with stronger invasion of T cells. Both cell types showed
no dependence on the matrix modifications. Microglia could be activated on the matrices
by lipopolysaccharide resulting in interleukin-6 and tumour necrosis factor-α
secretion. The findings herein indicate that biomimetic 3D matrices allow for cocultivation
and activation of primary microglia and T cells and provide useful tools
to study their interaction in vitro.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:93679 |
| Date | 11 September 2024 |
| Creators | Frühauf, Marie, Zeitschel, Ulrike, Höfling, Corinna, Ullm, Franziska, Rabiger, Friederike V., Alber, Gottfried, Pompe, Tilo, Müller, Uwe, Roßner, Steffen |
| Publisher | Wiley |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 10.1111/ejn.14978 |
Page generated in 0.0056 seconds