Dr Stefano Pluchino
Stem cell signalling and brain repair
Laboratory: Cambridge Stem Cell Institute, Clifford Allbutt Building, Cambridge Biomedical Campus. Departmental Affiliation: Clinical Neurosciences
Stefano Pluchino received his MD and PhD degrees at the University of Siena, Italy, and additional training at Cambridge University, UK.
He is University Reader in Regenerative Neuroimmunology (2016) and Honorary Consultant in Neurology. He’s also non-tenured Professor of Regenerative Neuroscience at the University Vita-Salute San Raffaele in Milano (Italy; since 2005) and adjunct Associate Professor in Neurology at the University of Vermont College of Medicine in Burlington (USA; since 2008).
Stefano Pluchino has been awarded 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). Dr Pluchino is a 2009 Italian Ministry of Health Young Investigator Awardee and 2010 European Research Council (ERC) Starting Independent Researcher and member of the Division of Stem Cell Neurobiology, within the Department of Clinical Neurosciences.
The major contribution of Stefano Pluchino’s studies has been the demonstration of the [constitutive vs inducible] immune modulatory functions of somatic neural stem cells (NSCs). His major recent focus has been the exploitation of the cellular and molecular mechanisms regulating the therapeutic plasticity of NSCs in inflammatory CNS diseases such as multiple sclerosis, ischemic stroke, and spinal cord injury. Current projects in his lab are exploring the different modalities by which transplanted NSCs engage programs of cell-to-cell communication with cells in the host microenvironment.
John and Lucille Van Geest Endowment, CDMRP MS Research Program, Italian MS Society (FISM), International Progressive MS Alliance, Wellcome Trust, European Commission, The Evelyn Trust, The Bascule Charitable Trust, The Great Britain Sakakawa Foundation, UK Regenerative Medicine Platform (UKRMP), Montreal Neurological Institute-University of Cambridge Fund, Wings for Life.
Transplanted iNSCs (green) migrate in the injured CNS accumulating close to reactive GFAP+ astrocytes (white), while differentiate into NeuN+ (red) neurons with fully formed spines. Nuclei are stained with DAPI (blue). (Credit Luca Peruzzotti-Jametti and Giulio Volpe)
My laboratory provided the first evidence of the immune modulatory functions of neural stem cells. This seminal observation led to pre-clinical studies where stem cells were injected through biological routes to protect the nervous system from secondary tissue damage. My group is now confronting with some key challenges that include:
- The development of protocols for safe human stem cells under standardized conditions;
- The choice of route of cell injection, cell dosage and cell type/stage;
- The identification of mechanisms of stem cell integration and signalling;
- The discovery of new biomarkers of stem cell survival, biodistribution and functional effects.
We are fully committed to delivering next-generation stem cell therapies into clinics for the treatment of highly invalidating neurological disorders that include multiple sclerosis, stroke and traumatic injuries of the brain/spinal cord.
Beatrice Balzarotti, Sara Bandiera, Joshua Bernstock, Alice Braga, Florian Gessler, Nunzio Iraci, Tommaso Leonardi, Giulia Manferrari, Dai Matsuse, Gioia Mingozzi, Emanuele Mauri, Luca Peruzzotti-Jametti, Jayden A. Smith, Jeroen Verheyen, Giulio Volpe.
In our lab we study how various types of stem cells and other advanced molecular therapies are able to help the damaged or diseased brain heal or even regenerate. In particular, we are clarifying the molecular mechanisms that transplanted stem cells use to interact with their surrounding tissue, the so-called microenvironment. Such mechanisms may be harnessed and used to modulate disease states in an effort to repair and/or regenerate critical components of the nervous system.
- G Volpe, JD Bernstock, L Peruzzotti-Jametti and S Pluchino. Modulation of host immune responses following non-hematopoietic stem cell transplants: Prospects for therapy in Progressive Multiple Sclerosis. J Neuroimmunol 2016 Dec 15. pii: S0165-5728(16)30312-5. doi: 10.1016/j.jneuroim.2016.12.005. [Epub ahead of print] (PMCID: 28034466);
- D Drago, V Basso, E Gaude, G Volpe, L Peruzzotti-Jametti, A Bachi, G Musco, A Andolfo, C Frezza, A Mondino and S Pluchino. Metabolic determinants of the immune modulatory function of neural stem cells. J Neuroinflammation 2016 Sep 2;13(1):232 (PMCID: 27590826);
- Cossetti C, Iraci N, Mercer TR, Leonardi T, Alpi E, Drago D, Alfaro-Cervello C, Saini H, Davis M, Schaeffer J, Muller W, Garcia-Verdugo JM, Mathivanan S, Bachi A, Enright A, Mattick JS, Pluchino S. Extracellular vesicles from neural stem cells transfer IFN-g via Ifngr1 to activate Stat1 signalling in target cells. Mol Cell 2014 Oct 23;56(2):193-204 PMCID:PMC4578249
- Pluchino S, Zanotti L, Rossi B, Brambilla E, Ottoboni L, Salani G, Martinello M, Cattalini A, Bergami A, Furlan R, Comi G, Constantin G, Martino G. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature. 2005; 436(7048): 266-71 PMID: 16015332
- Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, Galli R, Del Carro U, Amadio S, Bergami A, Furlan R, Comi G, Vescovi AL, Martino G. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature. 2003; 422(6933): 688-94 PMID: 12700753