Dr Stefano Pluchino University positionLecturer Dr Stefano Pluchino is pleased to consider applications from prospective PhD students. DepartmentsDepartment of Clinical Neurosciences InstitutesCambridge Centre for Brain Repair and MRC Cambridge Stem Cell Institute Home pagehttp://pluchino.brc.cam.ac.uk/labwiki... (personal home page) Research ThemesInterestsRecent evidence from our own laboratory indicates that the systemic injection of somatic neural stem/precursor cells (NPCs) very efficiently protect the CNS from the chronic degeneration induced by inflammation both in small rodents as well as in non-human primates affected by experimental MS, cerebral ischemic stroke, or contusion spinal cord injury (stem cell therapeutic plasticity). We are now exploring the cellular and molecular mechanisms regulating the therapeutic plasticity of stem cells in pre-clinical models of complex CNS diseases such as multiple sclerosis, and spinal cord injury. We are devoting special attention to the different modalities by which NPCs engage programs of horizontal cell-to-cell communication with cells in the microenvironment. Our major aim is to look into innate (physiological) mechanisms with the visionary focus of translating the knowledge of basal (vs reactive) stem cell functions into innovative high clinical impact therapeutics. ![Confocal microscopy image of two intravenously-injected ?-gal+ NPCs (green) persisting (110 days after cell injection) at the level of a representative CNS perivascular area from a R-EAE mouse in very close contact to CNS-infiltrating encephalitogenic blood-borne CD45+ inflammatory cells (red) [Nature 2005; 436: 266-71].](https://www.neuroscience.cam.ac.uk/uploadedFiles/pluchino_phpNqaXQc.jpg "Confocal microscopy image of two intravenously-injected ?-gal+ NPCs (green) persisting (110 days after cell injection) at the level of a representative CNS perivascular area from a R-EAE mouse in very close contact to CNS-infiltrating encephalitogenic blood-borne CD45+ inflammatory cells (red) [Nature 2005; 436: 266-71].") Confocal microscopy image of two intravenously-injected ?-gal+ NPCs (green) persisting (110 days after cell injection) at the level of a representative CNS perivascular area from a R-EAE mouse in very close contact to CNS-infiltrating encephalitogenic blood-borne CD45+ inflammatory cells (red) [Nature 2005; 436: 266-71]. Click image to view full-size Research Focus
EquipmentCell culture Cell transplantation Computational modelling Confocal microscopy Electron microscopy (scanning and transmission) Flow cytometry Fluorescence microscopy hES cells Immunohistochemistry In situ hybridization In vitro co-cultures Magnetic resonance imaging (MRI) Mathematical modeling Microscopy Non viral delivery technologies (nanoparticles; liposomes) Reverse engineering RNA deep sequencing Semi-quantitative real time RT-PCR siRNA Unbiased stereology Viral vector technology for cell engineering and ncRNA delivery Collaborators
Associated News Items
Key publicationsCusimano M, Biziato D, Brambilla E, Donegŕ M, Alfaro-Cervello C, Snider S, Salani G, Pucci F, Comi G, Garcia-Verdugo JM, De Palma M, Martino G, Pluchino S (2012), “Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord.” Brain Details Bacigaluppi M, Pluchino S, Peruzzotti Jametti L, Kilic E, Kilic U, Salani G, Brambilla E, West MJ, Comi G, Martino G, Hermann DM (2009), “Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms.” Brain 132(Pt 8):2239-51 Details Pluchino S, Gritti A, Blezer E, Amadio S, Brambilla E, Borsellino G, Cossetti C, Del Carro U, Comi G, 't Hart B, Vescovi A, Martino G (2009), “Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates.” Ann Neurol 66(3):343-54 Details Pluchino S, Zanotti L, Brambilla E, Rovere-Querini P, Capobianco A, Alfaro-Cervello C, Salani G, Cossetti C, Borsellino G, Battistini L, Ponzoni M, Doglioni C, Garcia-Verdugo JM, Comi G, Manfredi AA, Martino G (2009), “Immune regulatory neural stem/precursor cells protect from central nervous system autoimmunity by restraining dendritic cell function.” PLoS One 4(6):e5959 Details Pluchino S, Muzio L, Imitola J, Deleidi M, Alfaro-Cervello C, Salani G, Porcheri C, Brambilla E, Cavasinni F, Bergamaschi A, Garcia-Verdugo JM, Comi G, Khoury SJ, Martino G (2008), “Persistent inflammation alters the function of the endogenous brain stem cell compartment.” Brain 131(Pt 10):2564-78 Details 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 (2005), “Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism.” Nature 436(7048):266-71 Details 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. (2003), “Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis.” Nature Apr 17;422(6933):688-94 Publications2014Cerri F, Salvatore L, Memon D, Martinelli Boneschi F, Madaghiele M, Brambilla P, Del Carro U, Taveggia C, Riva N, Trimarco A, Lopez ID, Comi G, Pluchino S, Martino G, Sannino A, Quattrini A (2014), “Peripheral nerve morphogenesis induced by scaffold micropatterning.” Biomaterials 35(13):4035-45 Details Donegŕ M, Giusto E, Cossetti C, Schaeffer J, Pluchino S (2014), “Systemic injection of neural stem/progenitor cells in mice with chronic EAE.” J Vis Exp (86) Details L'Episcopo F, Tirolo C, Caniglia S, Testa N, Morale MC, Serapide MF, Pluchino S, Marchetti B (2014), “Targeting Wnt signaling at the neuroimmune interface for dopaminergic neuroprotection/repair in Parkinson's disease.” J Mol Cell Biol 6(1):13-26 Details L'Episcopo F, Tirolo C, Testa N, Caniglia S, Morale MC, Serapide MF, Pluchino S, Marchetti B (2014), “Wnt/?-Catenin Signaling Is Required to Rescue Midbrain Dopaminergic Progenitors and Promote Neurorepair in Ageing Mouse Model of Parkinson's Disease.” Stem Cells 32(8):2147-63 Details Peruzzotti-Jametti L, Donegá M, Giusto E, Mallucci G, Marchetti B, Pluchino S (2014), “The role of the immune system in central nervous system plasticity after acute injury.” Neuroscience Details Smith JA, Leonardi T, Huang B, Iraci N, Vega B, Pluchino S (2014), “Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases.” Biogerontology Details 2013Drago D, Cossetti C, Iraci N, Gaude E, Musco G, Bachi A, Pluchino S (2013), “The stem cell secretome and its role in brain repair.” Biochimie 95(12):2271-85 Details Giusto E, Donegŕ M, Cossetti C, Pluchino S (2013), “Neuro-immune interactions of neural stem cell transplants: From animal disease models to human trials.” Exp Neurol Details Hill AF, Pegtel DM, Lambertz U, Leonardi T, O'Driscoll L, Pluchino S, Ter-Ovanesyan D, Nolte-'t Hoen EN (2013), “ISEV position paper: extracellular vesicle RNA analysis and bioinformatics.” J Extracell Vesicles 2 Details L'Episcopo F, Tirolo C, Testa N, Caniglia S, Morale MC, Impagnatiello F, Pluchino S, Marchetti B (2013), “Aging-induced Nrf2-ARE pathway disruption in the subventricular zone drives neurogenic impairment in parkinsonian mice via PI3K-Wnt/?-catenin dysregulation.” J Neurosci 33(4):1462-85 Details Marchetti B, L'Episcopo F, Morale MC, Tirolo C, Testa N, Caniglia S, Serapide MF, Pluchino S (2013), “Uncovering novel actors in astrocyte-neuron crosstalk in Parkinson's disease: the Wnt/?-catenin signaling cascade as the common final pathway for neuroprotection and self-repair.” Eur J Neurosci 37(10):1550-63 Details Marchetti B, Pluchino S (2013), “Wnt your brain be inflamed? Yes, it Wnt!” Trends Mol Med 19(3):144-56 Details Pluchino S, Cossetti C (2013), “How stem cells speak with host immune cells in inflammatory brain diseases.” Glia 61(9):1379-401 Details Pluchino S, Peruzzotti-Jametti L (2013), “Rewiring the ischaemic brain with human-induced pluripotent stem cell-derived cortical neurons.” Brain 136(Pt 12):3525-7 Details 2012Bolton S, Hassall D, Hildebrand D, Brück W, Huang JK, Pluchino S, McKevitt T, Parry J, McFarlane M, Fagg R, Roulois A (2012), “Anti-inflammatory Disease Therapies: Challenges and Strategies in Drug Development.” Toxicol Pathol 40(1):122-5 Cossetti C, Alfaro-Cervello C, Donegŕ M, Tyzack G, Pluchino S (2012), “New perspectives of tissue remodelling with neural stem and progenitor cell-based therapies.” Cell Tissue Res Details Cossetti C, Smith JA, Iraci N, Leonardi T, Alfaro-Cervello C, Pluchino S (2012), “Extracellular membrane vesicles and immune regulation in the brain.” Front Physiol 3:117 Details Herz J, Reitmeir R, Hagen SI, Reinboth BS, Guo Z, Zechariah A, Elali A, Doeppner TR, Bacigaluppi M, Pluchino S, Kilic U, Kilic E, Hermann DM (2012), “Intracerebroventricularly delivered VEGF promotes contralesional corticorubral plasticity after focal cerebral ischemia via mechanisms involving anti-inflammatory actions.” Neurobiol Dis 45(3):1077-85 Details Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P, Askenase P, Bond VC, Borrŕs FE, Breakefield X, Budnik V, Buzas E, Camussi G, Clayton A, Cocucci E, Falcon-Perez JM, Gabrielsson S, Gho YS, Gupta D, Harsha HC, Hendrix A, Hill AF, Inal JM, Jenster G, Krämer-Albers EM, Lim SK, Llorente A, Lötvall J, Marcilla A, Mincheva-Nilsson L, Nazarenko I, Nieuwland R, Nolte-'t Hoen EN, Pandey A, Patel T, Piper MG, Pluchino S, Prasad TS, Rajendran L, Raposo G, Record M, Reid GE, Sánchez-Madrid F, Schiffelers RM, Siljander P, Stensballe A, Stoorvogel W, Taylor D, Thery C, Valadi H, van Balkom BW, Vázquez J, Vidal M, Wauben MH, Yáńez-Mó M, Zoeller M, Mathivanan S (2012), “Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation.” PLoS Biol 10(12):e1001450 Details L'episcopo F, Tirolo C, Testa N, Caniglia S, Morale MC, Deleidi M, Serapide MF, Pluchino S, Marchetti B (2012), “Plasticity of Subventricular Zone Neuroprogenitors in MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine) Mouse Model of Parkinson's Disease Involves Cross Talk between Inflammatory and Wnt/?-Catenin Signaling Pathways: Functional Consequences for Neuroprotection and Repair.” J Neurosci 32(6):2062-2085 Details 2011Cimadamore F, Fishwick K, Giusto E, Gnedeva K, Cattarossi G, Miller A, Pluchino S, Brill LM, Bronner-Fraser M, Terskikh AV (2011), “Human ESC-derived neural crest model reveals a key role for SOX2 in sensory neurogenesis.” Cell Stem Cell 8(5):538-51 Details L'episcopo F, Serapide MF, Tirolo C, Testa N, Caniglia S, Morale MC, Pluchino S, Marchetti B (2011), “A Wnt1 regulated Frizzled-1/?-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection.” Mol Neurodegener 6:49 Details Martino G, Pluchino S, Bonfanti L, Schwartz M (2011), “Brain regeneration in physiology and pathology: the immune signature driving therapeutic plasticity of neural stem cells.” Physiol Rev 91(4):1281-304 Details Pluchino S, Alfaro-Cervello C (2011), “Cyclooxygenase (COX)-1 takes control of adult hippocampal neurogenesis.” Cell Cycle 10(19):3229 Details Reitmeir R, Kilic E, Kilic U, Bacigaluppi M, ElAli A, Salani G, Pluchino S, Gassmann M, Hermann DM (2011), “Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity.” Brain 134(Pt 1):84-99 Details 2010Freedman MS, Bar-Or A, Atkins HL, Karussis D, Frassoni F, Lazarus H, Scolding N, Slavin S, Le Blanc K, Uccelli A, MSCT Study Group (2010), “The therapeutic potential of mesenchymal stem cell transplantation as a treatment for multiple sclerosis: consensus report of the International MSCT Study Group.” Mult Scler 16(4):503-10 Details 2009Gagliano N, Costa F, Cossetti C, Pettinari L, Bassi R, Chiriva-Internati M, Cobos E, Gioia M, Pluchino S (2009), “Glioma-astrocyte interaction modifies the astrocyte phenotype in a co-culture experimental model.” Oncol Rep 22(6):1349-56 Details Pluchino S, Zanotti L, Brini E, Ferrari S, Martino G (2009), “Regeneration and repair in multiple sclerosis: the role of cell transplantation.” Neurosci Lett 456(3):101-6 Details Shechter R, London A, Varol C, Raposo C, Cusimano M, Yovel G, Rolls A, Mack M, Pluchino S, Martino G, Jung S, Schwartz M (2009), “Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice.” PLoS Med 6(7):e1000113 Details 2008Bacigaluppi M, Pluchino S, Martino G, Kilic E, Hermann DM (2008), “Neural stem/precursor cells for the treatment of ischemic stroke.” J Neurol Sci 265(1-2):73-7 Details Butti E, Bergami A, Recchia A, Brambilla E, Del Carro U, Amadio S, Cattalini A, Esposito M, Stornaiuolo A, Comi G, Pluchino S, Mavilio F, Martino G, Furlan R (2008), “IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis.” Gene Ther 15(7):504-15 Details Pluchino S, Martino G (2008), “Neural stem cell-mediated immunomodulation: repairing the haemorrhagic brain.” Brain 131(Pt 3):604-5 Details Pluchino S, Martino G (2008), “The therapeutic plasticity of neural stem/precursor cells in multiple sclerosis.” J Neurol Sci 265(1-2):105-10 Details Serra PA, Pluchino S, Marchetti B, Desole MS, Miele E (2008), “The MPTP mouse model: cues on DA release and neural stem cell restorative role.” Parkinsonism Relat Disord 14 Suppl 2:S189-93 Details 2007Martino G, Pluchino S (2007), “Neural stem cells: guardians of the brain.” Nat Cell Biol 9(9):1031-4 Details 2006Amadio S, Pluchino S, Brini E, Morana P, Guerriero R, Boneschi FM, Comi G, Zaratin P, Muzio V, del Carro U (2006), “Motor evoked potentials in a mouse model of chronic multiple sclerosis.” Muscle Nerve 33(2):265-73 Details Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, Martino G, Schwartz M (2006), “Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells.” Mol Cell Neurosci 31(1):149-60 Details Capriles E, Do Campo A, Verde O, Pluchino S, Capriles Hulett A (2006), “Children's asthma and the third world: an approach.” J Investig Allergol Clin Immunol 16(1):11-8 Details Martino G, Pluchino S (2006), “The therapeutic potential of neural stem cells.” Nat Rev Neurosci 7(5):395-406 Details Ziv Y, Avidan H, Pluchino S, Martino G, Schwartz M (2006), “Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury.” Proc Natl Acad Sci U S A 103(35):13174-9 Details 2005Pluchino S, Bacigaluppi M, Bucello S, Butti E, Deleidi M, Zanotti L, Martino G, Furlan R (2005), “Gene and stem cell therapy for autoimmune demyelination.” Ernst Schering Res Found Workshop (53):133-46 Details Pluchino S, Martino G (2005), “The therapeutic use of stem cells for myelin repair in autoimmune demyelinating disorders.” J Neurol Sci 233(1-2):117-9 Details Pluchino S, Zanotti L, Deleidi M, Martino G (2005), “Neural stem cells and their use as therapeutic tool in neurological disorders.” Brain Res Brain Res Rev 48(2):211-9 Details 2004Furlan R, Butti E, Pluchino S, Martino G (2004), “Gene therapy for autoimmune diseases.” Curr Opin Mol Ther 6(5):525-36 Details 2003Furlan R, Brambilla E, Sanvito F, Roccatagliata L, Olivieri S, Bergami A, Pluchino S, Uccelli A, Comi G, Martino G (2003), “Vaccination with amyloid-beta peptide induces autoimmune encephalomyelitis in C57/BL6 mice.” Brain 126(Pt 2):285-91 Details Furlan R, Pluchino S, Marconi PC, Martino G (2003), “Cytokine gene delivery into the central nervous system using intrathecally injected nonreplicative viral vectors.” Methods Mol Biol 215:279-89 Details Furlan R, Pluchino S, Martino G (2003), “Gene therapy-mediated modulation of immune processes in the central nervous system.” Curr Pharm Des 9(24):2002-8 Details Furlan R, Pluchino S, Martino G (2003), “The therapeutic use of gene therapy in inflammatory demyelinating diseases of the central nervous system.” Curr Opin Neurol 16(3):385-92 Details Hernández Muńoz G, Pluchino S (2003), “Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer.” Maturitas 44 Suppl 1:S59-65 Details 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 (2003), “Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis.” Nature 422(6933):688-94 Details Pluchino S, Zanotti L, Martino G (2003), “Antibodies and myelination: facts and misacts.” Neurol Sci 24 Suppl 4:S231-3 Details 1997Annunziata P, Pluchino S, Martino T, Guazzi G (1997), “High levels of cerebrospinal fluid IgM binding to myelin basic protein are associated with early benign course in multiple sclerosis.” J Neuroimmunol 77(1):128-33 Details |