Ricerc@Sapienza

Conventional 2D cell cultures fail to represent the complexity of the brain and novel 3D systems are emerging as more realistic and representative models. However, available 3D brain models have important limitations due to the ¿self-assembling¿ process commonly used for their production, which generates a high degree of variability and reproducibility issues. 3D Bioprinting is an additive manufacturing technique that uses, as ink, a combination of biocompatible non-living materials and cells (bioink). This technique provides the possibility to combine cells in a controlled way, to build structures that closely mimic natural tissues. Human induced Pluripotent Stem Cells (iPSCs) can be derived from any individual by reprogramming body cells (e.g. skin, blood), which hence acquire the potential to be converted into any cell type of interest. Neurodevelopmental disorders such as Fragile X Syndrome (FXS) are widely studied using human iPSCs as a starting point to obtain specific neural population on which performing molecular and functional analysis. However, conventional culture fails to recapitulate the complex neural environment revealing itself a not reliable model system to fully characterize the pathology.
This project aims at generating novel 3D models of the human nervous system focusing on the brain cortex development and organization by using iPSC-derived neurons as `building block¿ of the model. Patient-derived 3D models of Fragile X Syndrome will be produced exploiting innovative 3D bioprinting methods in order to reproduce in vitro a more physiological condition to study the disorder. We will challenge these disease models to assess whether they can be used for drug testing and for developing new diagnostic tools. This work will fill an important gap in the pre-clinical development of new therapies for diseases of the nervous system, i.e. the inappropriateness of current in vitro models in terms of cellular cytoarchitecture and functional properties.