Stem cell- and nanomedicine-based regenerative approaches in spinal cord injuries: a proof-of-concept study

The research project aimed to validate a combinatorial therapeutic approach for spinal cord injuries based on neural stem cells transplant and nanomedicine tools. The final aim is to promote axonal regeneration after the injury through neural stem cell-replacement of lost tissue and enhancement of growth of transplanted cells by magnetic nano-pulling technology. The latter is based on loading cells with magnetic nanoparticles and, after the application of an external magnetic field, it is possible to induce forces (mechanical stimulation) on cells and manipulate their growth. For this project, we chose a specific type of neural stem cell: embryo-derived spinal cord patterned neuroepithelial stem cells (SC-NES cells). Different model systems (spinal cord organotypic model and cortical and spinal cord organoids/assembloids) were optimized and used to validate the proposed approach. The ability of magnetic nano-pulling to manipulate neural stem cell growth was assessed firstly in monolayer culture of SC-NES cells and then on the same cells transplanted into spinal cord organotypic slices. Elongation, networking and differentiation of SC-NES cells at first stages of differentiation were enhanced after mechanical stimulation for different time periods. Moreover, the generation of human cortico-spinal assembloid was optimized starting from human iPS cell, thus providing a platform for further validation of the proposed therapeutic approach. In the end, a part of the project aimed also to translate to in vivo models the magnetic nano-pulling technology through the design of magnetic device for mice with the help of engineering tools like 3D printing.