Novel Strategies for Cell-based Neural Reconstruction

Title Novel Strategies for Cell-based Neural Reconstruction
Acronym NSC-Reconstruct
Start date 2020-01-01
End date 2023-12-31
Sponsor European Commission
Institution University of Milan

Associated cell lines

Project Description

Neurodegenerative diseases and brain injuries affect large patient groups and carry large unmet clinical needs. NSCReconstruct will respond to these needs by developing innovative therapies based on cell replacement, cell reprogramming and circuit reconstruction that have the potential to transform how we treat a wide range of neurological diseases and disorders. In this area of clinical science European research has generated groundbreaking knowledge that has resulted in a pioneering human embryonic stem cell-derived product that is now entering clinical trials for Parkinson’s Disease (PD). In NSC-Reconstruct we will move beyond the replacement of a single neuronal type towards future cell therapies with enhanced authenticity, functions and compositions. NSC-Reconstruct will address PD as an example of disorder for which single neuron replacement has been developed. Our focus in PD will be on incorporating improved cell types and on local network reconstruction. We will also work on repairing long distance networks such as those affected in Huntington’s disease and finally in restoring the complex networks and projections of the cerebral cortex to achieve effective repair in conditions known to affect this structure, such as trauma or stroke. NSC-Reconstruct will lead to (i) the generation of neuronal types with clinically relevant functionality starting from human pluripotent stem cells or through in situ reprogramming, (ii) the optimization of donor cell composition through grafting of functional modules comprising distinct cell types capable of forming appropriate connections, (iii) the restoration of function through the reconstruction of these damaged connections and finally (iv) a greater understanding of the immunogenicity of grafted cells and how this can be minimized. Ultimately, NSC-Reconstruct will provide unique knowledge and products that will pave the way for future CNS cell replacement therapies using functionally enhanced and immune-tolerant cells.