Search Results - Pluchino, Stefano

Stefano Pluchino

Stefano Pluchino (born May 31, 1971) is Professor of Regenerative Neuroimmunology, within the Department of Clinical Neurosciences, at the University of Cambridge. His research studies whether the accumulation of neurological disability observed in patients with chronic inflammatory neurological conditions can be slowed down using next generation molecular therapies.

The overarching aim is to understand the basic mechanisms that allow exogenously delivered stem cells, gene therapy vectors and/or exosomes to create an environment that preserves damaged axons or prevents neurons from dying. Such mechanisms are being harnessed and used to modulate disease states to repair and/or regenerate critical components of the nervous system.

His research focuses on understanding and modifying the mechanisms underlying neurological disability in chronic inflammatory neurological conditions, with the aim of developing next-generation molecular therapies. His pioneering work established, through two landmark Nature papers, that adult neural stem cells (NSCs) could induce recovery in models of chronic multiple sclerosis (MS), laying the foundation for the regenerative neuroimmunology field. Since then, his research has delved into the mechanisms behind the therapeutic effects of NSCs, including their immunomodulatory and pro-regenerative properties.

Key discoveries from his lab include:

* Demonstrating how directly induced NSCs (iNSCs) respond to the immunometabolite succinate to suppress neuroinflammation, revealing a novel immune-metabolic crosstalk.

* Identifying mitochondrial complex I in microglia as a regulator of chronic CNS inflammation, providing a new metabolic target for neuroprotection and therapeutic intervention.

* Showing that iNSCs promote remyelination in chronic MS-like lesions by supporting endogenous repair mechanisms and directly generating myelin-producing cells.

His work on the interaction between stem cells and immune cells has demonstrated that advanced stem cell therapies exert their effects not only through cellular replacement but also via modulation of mitochondrial function and neuroinflammatory pathways. This perspective has inspired first-in-kind clinical trials of allogeneic neural stem cells in patients with progressive MS, including a pioneering Phase I trial demonstrating the safety and feasibility of intracerebroventricular NSC transplantation.

Further, his recent research employs advanced 2D and 3D stem cell models using patient-derived cells, revealing that neural progenitors from people with progressive MS exhibit a senescent, inflammatory phenotype that can be reversed with agents such as simvastatin. His lab also identified MS-specific epigenetic changes and a previously unrecognized population of immature, senescent, proinflammatory radial glia-like cells (DARGs), which spread inflammation and senescence, offering new avenues for personalized treatments.

Overall, Stefano Pluchino’s work integrates stem cell biology, neuroimmunology, immunometabolism, and patient-specific modelling to develop targeted therapies aimed at slowing or reversing MS progression. His insights into mitochondrial function, immune regulation, and regenerative strategies continue to shape cutting-edge approaches in neurodegenerative disease research with the goal of accessible, effective, patient-centred treatments. Provided by Wikipedia