3.8 Proceedings Paper

Micro structured tools for cell modeling in the fourth dimension

Publisher

SPIE-INT SOC OPTICAL ENGINEERING
DOI: 10.1117/12.2593332

Keywords

bioengineering; cell modeling; mechanobiology; optical imaging; microfluidics; metastasis; neurodegeneration; stem cell niche

Funding

  1. European Research Council (ERC project NICHOID) [646990]
  2. European Research Council (ERC project NICHOIDS) [754467]
  3. European Research Council (ERC project MOAB) [825159]
  4. European Commission (FET-OPEN project IN2SIGHT) [964481]
  5. European Space Agency (ESA project NICHOID-ET) [4000133244/20/NL/GLC]
  6. National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs projects MOAB) [NC/C01903/1, NC/C019201/1]
  7. Italian Ministry of University and Research (MIUR-FARE project BEYOND) [R16ZNN2R9K]
  8. Fondazione Social Venture Giordano Dell'Amore
  9. Cariplo Factory
  10. Politecnico di Milano
  11. Fondazione Bassetti
  12. Fondazione Triulza (S2P project 2021)
  13. European Research Council (ERC) [646990, 825159, 754467] Funding Source: European Research Council (ERC)

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The research team developed various bioengineered cell models to recapitulate different biological processes such as cartilage regeneration and bone metastasis formation. By using two-photon laser polymerization to fabricate micro scaffolds, they were able to control stem cell function and enhance their stemness and pluripotency. This opens up new possibilities for safer use of stem cells in therapy.
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.

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