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Stefano Pluchino

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Stefano Pluchino
Born (1971-05-31) May 31, 1971 (age 53)
Ragusa, Italy
Alma mater
Known for
Scientific career
Fields
  • Regenerative Medicine
  • Neuroscience
  • Neuroimmunology
  • Advanced Therapeutics
InstitutionsUniversity of Cambridge
Thesis Development of a neural stem cell-based therapy for experimental multiple sclerosis in mice  (2004)
Doctoral advisorGianvito Martino

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. [1] [2] [3] [4][5][6] 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.[1][3] Such mechanisms are being harnessed and used to modulate disease states to repair and/or regenerate critical components of the nervous system.

He is best known for having provided compelling evidence in support 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 contributed to reshape the classical view that advanced cell therapeutics (ACTs), including cellular grafts, may exert their therapeutic effects not only through structural cell replacement,[7] but also through modulation of mitochondrial function and neuroinflammatory pathways,[8][9][10][11][12] and has inspired the first-in-kind clinical trials of allogeneic somatic neural stem cells in patients with progressive MS.[13][14][15][16]

His most recent research has also elucidated the role of mitochondrial complex I activity in microglia, showcasing its pivotal role in sustaining neuroinflammation. This finding, as reported in a study published in Nature,[16] unveils a novel avenue for understanding the mechanisms underlying progressive multiple sclerosis (MS). The implications of this discovery are profound, as it suggests a new target for disease-modifying therapies. By targeting mitochondrial complex I activity in microglia, researchers may be able to intervene in the neuroinflammatory processes that contribute to disease progression in MS. This not only enhances our understanding of the pathophysiology of progressive MS but also opens avenues for the development of innovative treatments that could potentially halt or slow down disease progression.

His combined efforts towards the identification of new druggable targets, as well as the development of advanced regenerative therapies, underscore the importance of continued research into the intricate mechanisms underlying neurological diseases and the development of targeted therapies that can address these mechanisms.

Education

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Born in 1971, Pluchino grew up in Ragusa, Italy. He attended liceo classico Umberto I in Ragusa. He earned an M.D., a full residency in Neurology and a Ph.D. in Experimental Neurosciences from the University of Siena, Italy (joint with San Raffaele Scientific Institute, Milan), under the mentorship of Gianvito Martino in 2004.[17][18][19] The title of his PhD thesis was ‘Development of a neural stem cell-based therapy for experimental multiple sclerosis in mice’.

He then completed his post-doctoral research at San Raffaele Scientific Institute, and Vita-Salute San Raffaele University, Milan. He was also an instructor in Experimental Neurosciences at University Vita-Salute San Raffaele, Milan until 2010.

In 2010, Pluchino joined the faculty at the University of Cambridge – School of Clinical Medicine, with a laboratory at the Van Geest Centre for Brain Repair, on the Forvie site of the Cambridge Biomedical Campus. He became University Lecturer and Honorary Consultant in Neurology, as well as principal investigator at the Wellcome–MRC Cambridge Stem Cell Institute. He was promoted to University Reader in Regenerative Neuroimmunology in 2016. In 2021, Pluchino was further promoted to Professor of Regenerative Neuroimmunology, in the Department of Clinical Neurosciences.[20]

Research and career

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Pluchino's 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.[7][9][21][12] The overarching aim is to understand the basic mechanisms that allow exogenously delivered stem cells, gene therapy vectors and/or exosomes[22][23][24][8][25] to create an environment that preserves damaged axons or prevents neurons from dying.[12][11][26] Such mechanisms may be harnessed and used to modulate disease states to repair and/or regenerate critical components of the nervous system.[10][27][13][28]

In addition to his positions in the Department of Clinical Neurosciences at the University of Cambridge, Pluchino serves as Chair of the Scientific Advisory Board at ReNeuron lcc.[29]

Awards and honors

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  • 2003 AINI Award
  • 2003 European Charcot Foundation (ECF) Award
  • 2004 SIICA Award
  • 2006 Serono Foundation Multiple Sclerosis Award;
  • 2007 FISM Rita Levi-Montalcini Award;
  • 2008 Regional Agency for Instruction, Formation and Work (ARIFL) Research and Internationalization Award;
  • 2010 Royan International Research Award;

References

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  1. ^ a b "Stefano Pluchino - How stem cells speak with immune cells". YouTube. 26 January 2015.
  2. ^ "Cambridge Neuroscience - Stefano Pluchino - Regenerative Neuroimmunology: a stem cell perspective". YouTube. 8 June 2021.
  3. ^ a b "How Exosomes Are Revolutionizing Neuroimmunology with Dr. Pluchino". BioInformant. 29 June 2018.
  4. ^ Genovese, Giovanna (10 March 2018). "Lotta "personalizzata" con staminali alla sclerosi multipla: tre "cervelli" siciliani ci stanno lavorando". La Sicilia (in Italian).
  5. ^ "Sclerosi multipla, staminali domano l'infiammazione". Giornale di Sicilia (in Italian). 26 February 2018.
  6. ^ "Using stem cells to tackle CNS disorders: an interview with Dr Stefano Pluchino". News-Medical.net. 5 January 2016.
  7. ^ a b 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, A L; Martino, G (April 2003). "Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis". Nature. 422 (6933): 688–694. Bibcode:2003Natur.422..688P. doi:10.1038/nature01552. PMID 12700753. S2CID 4412113.
  8. ^ a b Peruzzotti-Jametti, L; Bernstock, J D; Vicario, N; Costa, A S.H.; Kwok, C K; Leonardi, T; Booty, L M; Bicci, I; Balzarotti, B; Volpe, G (March 2018). "Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation". Cell Stem Cell. 22 (3): 355–368. doi:10.1016/j.stem.2017.11.020. PMC 5757249. PMID 29304344.
  9. ^ a b 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 (July 2005). "Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism". Nature. 436 (7048): 266–271. Bibcode:2005Natur.436..266P. doi:10.1038/nature03889. PMID 16015332. S2CID 4416083.
  10. ^ a b 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 (September 2009). "Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates". Ann Neurol. 66 (3): 343–354. doi:10.1002/ana.21754. PMID 19798638. S2CID 42755439.
  11. ^ a b Cusimano, M; Biziato, D; Brambilla, E; Donegà, M; Alfaro-Cervello, C; Snider, S; Salani, G; Pucci, F; Comi, G; Garcia-Verdugo, J M; De Palma, M; Martino, G; Pluchino, S (February 2012). "Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord". Brain. 135 (Pt 2): 447–460. doi:10.1093/brain/awr331. PMC 3286199. PMID 22232595.
  12. ^ a b c Bacigaluppi, M; Pluchino, S; Peruzzotti-Jametti, L; Kilic, E; Kilic, U; Salani, G; Brambilla, E; West, M J; Comi, G; Martino, G; Hermann, D M (August 2009). "Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms" (PDF). Brain. 132 (Pt 8): 2239–2251. doi:10.1093/brain/awp174. PMID 19617198.
  13. ^ a b Leone MA; Gelati M; Profico DC; Gobbi C; Pravatà E; Copetti M; Conti C; Abate L; Amoruso L; Apollo F; Balzano RF; Bicchi I; Carella M; Ciampini A; Colosimo C; Crociani P; D'Aloisio G; Di Viesti P; Ferrari D; Fogli D; Fontana A; Frondizi D; Grespi V; Kuhle J; Laborante A; Lombardi I; Muzi G; Paci F; Placentino G; Popolizio T; Ricciolini C; Sabatini S; Silveri G; Spera C; Stephenson D; Stipa G; Tinella E; Zarrelli M; Zecca C; Ventura Y; D'Alessandro A; Peruzzotti-Jametti L; Pluchino S; Vescovi AL (December 7, 2023). "Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis". Cell Stem Cell. 30 (12): 1597–1609.e8. doi:10.1016/j.stem.2023.11.001. hdl:10281/453838. PMID 38016468.
  14. ^ Fossati, V; Peruzzotti-Jametti, L; Pluchino, S (2023). "A neural stem-cell treatment for progressive multiple sclerosis". Nat Med. 29 (1): 27–28. doi:10.1038/s41591-022-02164-9. PMID 36639562.
  15. ^ Genchi, A; Brambilla, E; Sangalli, F; Radaelli, M; Bacigaluppi, M; Furlan, R; Andolfo, A; Drago, D; Magagnotti, C; Scotti, GM (2023). "Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study". Nat Med. 29 (1): 75–85. doi:10.1038/s41591-022-02097-3. hdl:2434/965336. PMC 9873560. PMID 36624312.
  16. ^ a b Peruzzotti-Jametti, L; Willis, CM; Krzak, G; Hamel, R; Pirvan, L; Ionescu, RB; Reisz, JA; Prag, HA; Garcia-Segura, ME; Wu, V (2024). "Mitochondrial complex I activity in microglia sustains neuroinflammation". Nature. 628 (8006): 195–203. Bibcode:2024Natur.628..195P. doi:10.1038/s41586-024-07167-9. PMC 10990929. PMID 38480879.
  17. ^ "Stefano Pluchino". Neurology Academy.
  18. ^ "Stefano Pluchino". www.eurostemcell.org.
  19. ^ "ORCID". orcid.org.
  20. ^ "Member: Stefano Pluchino". Cambridge Neuroscience.
  21. ^ Pluchino, S; Muzio, L; Imitola, J; Deleidi, M; Alfaro-Cervello, C; Salani, G; Porcheri, C; Brambilla, E; Cavasinni, F; Bergamaschi, A; Garcia-Verdugo, J M; Comi, G; Khoury, S J; Martino, G (October 2008). "Persistent inflammation alters the function of the endogenous brain stem cell compartment". Brain. 131 (Pt 10): 2564–2578. doi:10.1093/brain/awn206. PMID 18765417.
  22. ^ Kalra, H; Simpson, R J; Ji, H; Aikawa, E; Altevogt, P; Askenase, P; Bond, V C; Borràs, F E; Breakefield, X; Budnik, V; Buzas, E I; Camussi, G; Clayton, A; Cocucci, E; Falcon-Perez, J M; Gabriel, S; Gho, Y S; Gupta, D; Harsha, H C; Hendrix, A; Hill, A F; Inal, J M; Jenster, G; Krämer-Albers, E M; Lim, S K; Llorente, A; Lötvall, J; Marcilla, A; Mincheva-Nilsson, L; Nazarenko, I; Nieuwland, R; Nolte-'t Hoen, E N; Pandey, A; Patel, T; Piper, M G; Pluchino, S; Prasad, T S K; Rajendran, L; Raposo, G; Record, M; Reid, G E; Sánchez-Madrid, F; Schiffelers, R M; Siljander, P; Stensballe, A; Stoorvogel, W; Taylor, D; Thery, C; Valadi, H; van Balkom, B W; Vázquez, J; Vidal, M; Wauben, M H M; Yáñez-Mó, M; Zoeller, M (December 2012). "Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation". PLOS Biol. 10 (12): e1001450. doi:10.1371/journal.pbio.1001450. PMC 3525526. PMID 23271954.
  23. ^ Cossetti, C; Iraci, N; Mercer, T R; Leonardi, T; Alpi, E; Drago, D; Alfaro-Cervello, C; Saini, H K; Davis, M; Schaeffer, J; Muller, W; Garcia-Verdugo, J M; Mathivanan, S; Bachi, A; Enright, A; Mattick, J S; Pluchino, S (April 2014). "Extracellular vesicles from neural stem cells transfer IFN-g via Ifngr1 to activate Stat1 signalling in target cells". Molecular Cell. 56 (2): 193–204. doi:10.1016/j.molcel.2014.08.020. PMC 4578249. PMID 25242146.
  24. ^ Iraci, N; Gaude, E; Leonardi, T; Costa, A S.H.; Cossetti, C; Saini, H K; Enright, A; Frezz, C; Pluchino, S (September 2017). "Extracellular vesicles are independent metabolic units delivering functional Asparaginase-like protein 1". Nature Chemical Biology. 13 (9): 951–955. doi:10.1038/nchembio.2422. PMC 5563455. PMID 28671681.
  25. ^ Peruzzotti-Jametti, L; Bernstock, JD; Willis, CM; Manferrari, G; Rogall, R; Fernandez-Vizarra, E; Williamson, JC; Braga, A; van den Bosch, A; Leonardi, T; Krzak, G; Kittel, A; Benincá, C; Vicario, N; Tan, S; Bastos, C; Bicci, I; Iraci, N; Smith, JA; Peacock, B; Muller, KH; Lehner, PJ; Buzas, EI; Faria, N; Zeviani, M; Frezza, C; Brisson, A; Matheson, NJ; Viscomi, C; Pluchino, S (September 2021). "Neural stem cells traffic functional mitochondria via extracellular vesicles" (PDF). PLOS Biol. 19 (9): e3001166. doi:10.1371/journal.pbio.3001166. PMC 8055036. PMID 33826607.
  26. ^ Smith, J A; Braga, A; Verheyen, J; Basilico, S; Alfaro-Cervello, C; Peruzzotti-Jametti, L; Haque, F; Guo, P; Pluchino, S (March 2018). "RNA nanotherapeutics for the amelioration of astroglial reactivity". Mol Ther Nucleic Acids. 10: 103–121. doi:10.1016/j.omtn.2017.11.008. PMC 5738063. PMID 29499926.
  27. ^ Braga, A; Bandiera, S; Verheyen, J; Hamel, R; Rutigliani, C; Edenhofer, F; Smith, J A; Pluchino, S (December 2020). "Combination of in situ Lcn2 pRNA-RNAi nanotherapeutics and iNSC transplantation ameliorates experimental spinal cord injury in mice". Mol Ther. 28 (12): 2677–2690. doi:10.1016/j.ymthe.2020.08.001. PMC 7704756. PMID 32877696.
  28. ^ "Multiple sclerosis breakthrough could lead to treatments that halt disease's progression". ITV News.
  29. ^ "ReNeuron appoints new scientific advisory board". Proactiveinvestors UK. 3 April 2023.
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