Stefano Pluchino, MD, PhD

Stefano Pluchino is Clinical Professor of Regenerative Neuroimmunology and Honorary Consultant in Neurology, within the Department of Clinical Neurosciences, University of Cambridge, UK. He obtained his MD and PhD in Experimental Neuroscience at the University of Siena (Italy) and progressed towards two consecutive post docs and then a tenured Group Leader position at the San Raffaele Scientific Institute in Milan (Italy), before moving to Cambridge in 2010.

 

The Pluchino Lab studies whether the accumulation of neurological disability observed in patients with chronic inflammatory neurological conditions can be slowed, prevented, or reversed using next-generation molecular and cell-based therapies. The research operates across the full translational spectrum — from mechanistic discovery in murine and human disease models, through patient-derived stem cell platforms, to first-in-human clinical trials. The overarching aim is to understand the fundamental mechanisms by which exogenously delivered stem cells, extracellular vesicles (EVs), gene therapy vectors, and pharmacological agents create an environment that preserves damaged axons, prevents neuronal death, and promotes remyelination and CNS repair. Such mechanisms may be harnessed to modulate disease states and repair and regenerate critical components of the nervous system. By understanding the mechanisms of intercellular neuro-immune signalling, diseases of the central nervous system (CNS) may be treated more effectively, and significant neuroprotection may be achieved with new tailored molecular therapeutics.

 

Stefano Pluchino is best known for having provided compelling evidence of the feasibility and efficacy of advanced stem cell therapies in rodent and non-human primate models of inflammatory neurological diseases, including multiple sclerosis. His work has fundamentally reshaped the classical view that advanced cell therapeutics (ACTs) exert their therapeutic effects only through structural cell replacement, demonstrating instead that they act through a rich repertoire of mechanisms, including immunomodulation, neurotrophic support, modulation of mitochondrial function, and metabolic crosstalk with the host inflammatory environment. This body of preclinical work directly inspired and informed the first-in-human Phase I clinical trial of intracerebroventricular transplantation of allogeneic somatic neural stem cells in patients with secondary progressive MS — which Stefano co-led — demonstrating safety and early signs of biological activity (Cell Stem Cell, 2023). He currently serves as Principal Investigator of the RESTORE consortium (IPMS Alliance, 2025), and co-leads the MS-STAT2 Phase III trial and the OCTOPUS adaptive platform trial, forming a coherent clinical pipeline aimed at transforming the outlook for people living with progressive MS.

 

A further landmark contribution has been the elucidation of mitochondrial complex I activity in microglia as a key driver of chronic neuroinflammation. Reported in Nature (2024), this work demonstrated that mitochondrial complex I sustains aberrant microglial activation through reverse electron transport and reactive oxygen species production — a finding validated in human MS tissue. Pharmacological inhibition of this pathway conferred neuroprotection and improved functional outcomes in preclinical models, identifying microglial complex I as a novel druggable target for progressive MS. This not only enhances our understanding of the pathophysiology of progressive MS but also opens avenues for developing innovative treatments that could halt or slow disease progression.

 

Most recently, the Pluchino Lab has pioneered the development of patient-derived stem cell platforms as a frontier tool to interrogate MS pathobiology. These models — integrating iPSC-derived neural systems, single-cell multi-omics, epigenetic profiling, and advanced 2D/3D organoid approaches — have uncovered novel patient-specific disease mechanisms, including dysregulated cholesterol metabolism and aberrant interferon signalling in MS patient-derived neural stem cells, as well as an accelerated cellular ageing phenotype that may contribute to smouldering neuroinflammation (Cell Stem Cell 2024; Neuron 2025). These platforms serve simultaneously as discovery engines for identifying new therapeutic targets and as testbeds for refining next-generation interventions, embodying a vision of stem cell technology as both a powerful research instrument and a potential cure.

 

Stefano Pluchino is recipient of numerous national and international awards, among which the Italian Multiple Sclerosis Foundation (FISM) Rita Levi-Montalcini prize for outstanding research in MS (2007) and the International Royan Award for outstanding research in Stem Cell Biology and Technology (2010). He is a 2009 Italian Ministry of Health Young Investigator Awardee and 2010 European Research Council (ERC) Starting Independent Researcher. More recently, he was awarded the International Progressive MS Alliance Experimental Medicine Development Award (2025), reflecting the sustained international recognition of his translational research programme.

 

His laboratory research on Regenerative Neuroimmunology is documented in >240 publications in international journals, including many recent articles in highly prestigious journals such as Nature, Cell, Cell Stem Cell, Nat Cell Biol, Nat Chem Biol, PNAS, PLoS Biol, PLoS Med, Brain, Ann Neurol, and J Neurosci, as well as invited review articles in Nat Rev Neurosci, Physiol Reviews, Trends Mol Med, and Trends Immunol. Recent landmark publications include contributions to The Lancet (2025), Neuron (2025), and Cell Stem Cell (2023, 2024), reflecting the sustained high-impact trajectory of his research programme. His publications have to date received >21,500 citations (ISI-WOK), with a Hirsch Factor of 68.

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email: spp24@cam.ac.uk

Tel.: +44 1223 331163 (office)

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