Micro structured tools for cell modeling in the fourth dimension

We describe several bioengineered cell models developed by our group. We develop tools for cell culture allowing fluorescence diagnostics on the cellularised constructs cultured within, both in 3D and prolonged culture times extending to several weeks. These cell models proved able to recapitulate in vitro several slowly developing biological processes such as the regeneration of a cartilaginous tissue by cartilage cells, the formation of a bone metastasis by breast cancer cells, the instruction of adaptive immune cells as occurs in a lymphnode, and the neuroprotective effect on pathological neurons of mesenchymal stem cell secretome. We also scaled down these tools in the aim to better control stem cell function in our models, by applying two-photon laser polymerization to fabricate micro scaffolds for stem cell expansion. We were able to condition mesenchymal stem cells, neural precursor cells and embryonic stem cells towards maintenance of a greater stemness and multipotency/pluripotency, compared to conventional flat culture. This result opens an avenue towards a safer use of these cells for stem cells therapies. Finally, we describe our new revolutionary concept of implanting the cell model in a living organism to regenerate a vascularized network anastomosed to the host, allowing for studies involving interactions with the host immune system.