Stefano Pluchino

{{Short description|Italian researcher}}

{{BLP primary sources|date=January 2024}}

{{Infobox scientist

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| name = Stefano Pluchino

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| birth_place = Ragusa, Italy

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| fields = {{Plainlist|

  • Regenerative Medicine
  • Neuroscience
  • Neuroimmunology
  • Advanced Therapeutics

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| workplaces = University of Cambridge

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| thesis_title = Development of a neural stem cell-based therapy for experimental multiple sclerosis in mice

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| thesis_year = 2004

| doctoral_advisor = Gianvito Martino

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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.

{{cite web |title=Stefano Pluchino - How stem cells speak with immune cells | website=YouTube | date=26 January 2015 |url=https://www.youtube.com/watch?v=PU27OrONMrE |language=en}}

{{cite web |title=Cambridge Neuroscience - Stefano Pluchino - Regenerative Neuroimmunology: a stem cell perspective | website=YouTube | date=8 June 2021 |url=https://www.youtube.com/watch?v=g86ZN-rE3qM |language=en}}

{{cite web |title=How Exosomes Are Revolutionizing Neuroimmunology with Dr. Pluchino |url=https://bioinformant.com/dr-stefano-pluchino/ |website=BioInformant |date=29 June 2018}}

{{cite web |last1=Genovese |first1=Giovanna |title=Lotta "personalizzata" con staminali alla sclerosi multipla: tre "cervelli" siciliani ci stanno lavorando |url=https://www.lasicilia.it/sicilians/lotta-personalizzata-con-staminali-alla-sclerosi-multipla-tre-cervelli-siciliani-ci-stanno-lavorando-890815/ |website=La Sicilia |language=it-IT |date=10 March 2018}}{{cite web |title=Sclerosi multipla, staminali domano l'infiammazione |url=https://gds.it/speciali/scienza-tecnica/2018/02/26/sclerosi-multipla-staminali-domano-l-infiammazione-9cc9f459-c421-45b4-95f9-abca475a5948/ |website=Giornale di Sicilia |language=it |date=26 February 2018}}{{cite web |title=Using stem cells to tackle CNS disorders: an interview with Dr Stefano Pluchino |url=https://www.news-medical.net/news/20160105/Using-stem-cells-to-tackle-CNS-disorders-an-interview-with-Dr-Stefano-Pluchino.aspx |website=News-Medical.net |language=en |date=5 January 2016}} 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.

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, but also through modulation of mitochondrial function and neuroinflammatory pathways, and has inspired the first-in-kind clinical trials of allogeneic somatic neural stem cells in patients with progressive MS.

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, 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

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.{{cite web |url=https://neurologyacademy.org/profiles/dr-stefano-pluchino |title=Stefano Pluchino|website=Neurology Academy |language=en}}{{cite web |url=https://www.eurostemcell.org/it/stefano-pluchino |website=www.eurostemcell.org|title=Stefano Pluchino}}{{cite web |title=ORCID |url=https://orcid.org/0000-0002-6267-9472 |website=orcid.org}} 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 [https://www.brc.cam.ac.uk/ 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.{{cite web |title=Member: Stefano Pluchino |url=https://neuroscience.cam.ac.uk/member/pluchino/ |website=Cambridge Neuroscience |language=en}}

Research and career

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. 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 may be harnessed and used to modulate disease states to repair and/or regenerate critical components of the nervous system.{{cite web |title=Multiple sclerosis breakthrough could lead to treatments that halt disease's progression |url=https://www.itv.com/news/2023-11-27/ms-breakthrough-could-lead-to-treatments-that-halt-diseases-progression |website=ITV News}}

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.{{cite web |title=ReNeuron appoints new scientific advisory board |url=https://www.proactiveinvestors.co.uk/companies/news/1011008/reneuron-appoints-new-scientific-advisory-board-1011008.html |website=Proactiveinvestors UK |language=en |date=3 April 2023}}

Awards and honors

  • 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

{{cite journal |last1=Pluchino |first1=S |last2=Quattrini |first2=A |last3=Brambilla |first3=E |last4=Gritti |first4=A |last5=Salani |first5=G |last6=Dina |first6=G |last7=Galli |first7=R |last8=Del Carro |first8=U |last9=Amadio |first9=S |last10=Bergami |first10=A |last11=Furlan |first11=R |last12=Comi |first12=G |last13=Vescovi |first13=A L |last14=Martino |first14=G |title=Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis |journal=Nature |date=April 2003 |volume=422 |issue=6933 |pages=688–694 |doi=10.1038/nature01552|pmid=12700753 |bibcode=2003Natur.422..688P |s2cid=4412113 }}

{{cite journal |last1=Pluchino |first1=S |last2=Zanotti |first2=L |last3=Rossi |first3=B |last4=Brambilla |first4=E |last5=Ottoboni |first5=L |last6=Salani |first6=G |last7=Martinello |first7=M |last8=Cattalini |first8=A |last9=Bergami |first9=A |last10=Furlan |first10=R |last11=Comi |first11=G |last12=Constantin |first12=G |last13=Martino |first13=G |title=Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism |journal=Nature |date=July 2005 |volume=436 |issue=7048 |pages=266–271 |doi=10.1038/nature03889|pmid=16015332 |bibcode=2005Natur.436..266P |s2cid=4416083 }}

{{cite journal |last1=Pluchino |first1=S |last2=Muzio |first2=L |last3=Imitola |first3=J |last4=Deleidi |first4=M |last5=Alfaro-Cervello |first5=C |last6=Salani |first6=G |last7=Porcheri |first7=C |last8=Brambilla |first8=E |last9=Cavasinni |first9=F |last10=Bergamaschi |first10=A |last11=Garcia-Verdugo |first11=J M |last12=Comi |first12=G |last13=Khoury |first13=S J |last14=Martino |first14=G |title=Persistent inflammation alters the function of the endogenous brain stem cell compartment |journal=Brain |date=October 2008 |volume=131 |issue=Pt 10 |pages=2564–2578 |doi=10.1093/brain/awn206|pmid=18765417 }}

{{cite journal |last1=Bacigaluppi |first1=M |last2=Pluchino |first2=S |last3=Peruzzotti-Jametti |first3=L |last4=Kilic |first4=E |last5=Kilic |first5=U |last6=Salani |first6=G |last7=Brambilla |first7=E |last8=West |first8=M J |last9=Comi |first9=G |last10=Martino |first10=G |last11=Hermann |first11=D M |title=Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms |journal=Brain |date=August 2009 |volume=132 |issue=Pt 8 |pages=2239–2251 |doi=10.1093/brain/awp174|pmid=19617198 |url=https://www.zora.uzh.ch/id/eprint/155215/1/ZORA_NL_155215.pdf }}

{{cite journal |last1=Pluchino |first1=S |last2=Gritti |first2=A |last3=Blezer |first3=E |last4=Amadio |first4=S |last5=Brambilla |first5=E |last6=Borsellino |first6=G |last7=Cossetti |first7=C |last8=Del Carro |first8=U |last9=Comi |first9=G |last10='t Hart |first10=B |last11=Vescovi |first11=A |last12=Martino |first12=G |title=Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates |journal=Ann Neurol |date=September 2009 |volume=66 |issue=3 |pages=343–354 |doi=10.1002/ana.21754|pmid=19798638 |s2cid=42755439 }}

{{cite journal |last1=Cusimano |first1=M |last2=Biziato |first2=D |last3=Brambilla |first3=E |last4=Donegà |first4=M |last5=Alfaro-Cervello |first5=C |last6=Snider |first6=S |last7=Salani |first7=G |last8=Pucci |first8=F |last9=Comi |first9=G |last10=Garcia-Verdugo |first10=J M |last11=De Palma |first11=M |last12=Martino |first12=G |last13=Pluchino |first13=S |title=Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord |journal=Brain |date=February 2012 |volume=135 |issue=Pt 2 |pages=447–460 |doi=10.1093/brain/awr331|pmid=22232595 |pmc=3286199 }}

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{{cite journal |last1=Cossetti |first1=C |last2=Iraci |first2=N |last3=Mercer |first3=T R |last4=Leonardi |first4=T |last5=Alpi |first5=E |last6=Drago |first6=D |last7=Alfaro-Cervello |first7=C |last8=Saini |first8=H K |last9=Davis |first9=M |last10=Schaeffer |first10=J |last11=Muller |first11=W |last12=Garcia-Verdugo |first12=J M |last13=Mathivanan |first13=S |last14=Bachi |first14=A |last15=Enright |first15=A |last16=Mattick |first16=J S |last17=Pluchino |first17=S |title=Extracellular vesicles from neural stem cells transfer IFN-g via Ifngr1 to activate Stat1 signalling in target cells |journal=Molecular Cell |date=April 2014 |volume=56 |issue=2 |pages=193–204 |doi=10.1016/j.molcel.2014.08.020|doi-access=free |pmid=25242146 |pmc=4578249 }}

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{{cite journal |title=Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis |author1=Leone MA |author2=Gelati M |author3=Profico DC |author4=Gobbi C |author5=Pravatà E |author6=Copetti M |author7=Conti C |author8=Abate L |author9=Amoruso L |author10=Apollo F |author11=Balzano RF |author12=Bicchi I |author13=Carella M |author14=Ciampini A |author15=Colosimo C |author16=Crociani P |author17=D'Aloisio G |author18=Di Viesti P |author19=Ferrari D |author20=Fogli D |author21=Fontana A |author22=Frondizi D |author23=Grespi V |author24=Kuhle J |author25=Laborante A |author26=Lombardi I |author27=Muzi G |author28=Paci F |author29=Placentino G |author30=Popolizio T |author31=Ricciolini C |author32=Sabatini S |author33=Silveri G |author34=Spera C |author35=Stephenson D |author36=Stipa G |author37=Tinella E |author38=Zarrelli M |author39=Zecca C |author40=Ventura Y |author41=D'Alessandro A |author42=Peruzzotti-Jametti L |author43=Pluchino S |author44=Vescovi AL |journal=Cell Stem Cell |date=December 7, 2023 |volume=30 |issue=12 |pages=1597–1609.e8 |doi=10.1016/j.stem.2023.11.001 |pmid=38016468|doi-access=free |hdl=10281/453838 |hdl-access=free }}

{{cite journal |last1=Fossati |first1=V |last2=Peruzzotti-Jametti |first2=L |last3=Pluchino |first3=S |title=A neural stem-cell treatment for progressive multiple sclerosis |journal=Nat Med |date=2023 |volume=29 |issue=1 |pages=27–28 |doi=10.1038/s41591-022-02164-9|pmid=36639562 }}

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{{cite journal |last1=Peruzzotti-Jametti |first1=L |last2=Willis |first2=CM |last3=Krzak |first3=G |last4=Hamel |first4=R |last5=Pirvan |first5=L |last6=Ionescu |first6=RB |last7=Reisz |first7=JA |last8=Prag |first8=HA |last9=Garcia-Segura |first9=ME |last10=Wu |first10=V |title=Mitochondrial complex I activity in microglia sustains neuroinflammation |journal=Nature |date=2024 |volume=628 |issue=8006 |pages=195–203 |doi=10.1038/s41586-024-07167-9|pmid=38480879 |pmc=10990929 |bibcode=2024Natur.628..195P }}