24 results on '"Butti, Erica"'
Search Results
2. Harmonization of sensorimotor deficit assessment in a registered multicentre pre-clinical randomized controlled trial using two models of ischemic stroke
- Author
-
Valente, Alessia, Mariani, Jacopo, Seminara, Serena, Tettamanti, Mauro, Pignataro, Giuseppe, Perego, Carlo, Sironi, Luigi, Pedata, Felicita, Amantea, Diana, Bacigaluppi, Marco, Vinciguerra, Antonio, Diamanti, Susanna, Viganò, Martina, Santangelo, Francesco, Zoia, Chiara Paola, Rodriguez-Menendez, Virginia, Castiglioni, Laura, Rzemieniec, Joanna, Dettori, Ilaria, Bulli, Irene, Coppi, Elisabetta, Di Santo, Chiara, Cuomo, Ornella, Gullotta, Giorgia Serena, Butti, Erica, Bagetta, Giacinto, Martino, Gianvito, De Simoni, Maria-Grazia, Ferrarese, Carlo, Fumagalli, Stefano, and Beretta, Simone
- Published
- 2023
- Full Text
- View/download PDF
3. Neural precursor cells tune striatal connectivity through the release of IGFBPL1
- Author
-
Butti, Erica, Cattaneo, Stefano, Bacigaluppi, Marco, Cambiaghi, Marco, Scotti, Giulia Maria, Brambilla, Elena, Ruffini, Francesca, Sferruzza, Giacomo, Ripamonti, Maddalena, Simeoni, Fabio, Cacciaguerra, Laura, Zanghì, Aurora, Quattrini, Angelo, Fesce, Riccardo, Panina-Bordignon, Paola, Giannese, Francesca, Cittaro, Davide, Kuhlmann, Tanja, D’Adamo, Patrizia, Rocca, Maria Assunta, Taverna, Stefano, and Martino, Gianvito
- Published
- 2022
- Full Text
- View/download PDF
4. Neural precursor cell-secreted TGF-[beta]2 redirects inflammatory monocyte-derived cells in CNS autoimmunity
- Author
-
De Feo, Donatella, Merlini, Arianna, Brambilla, Elena, Ottoboni, Linda, Laterza, Cecilia, Menon, Ramesh, Srinivasan, Sundararajan, Farina, Cinthia, Manuel Garcia Manteiga, Jose, Butti, Erica, Bacigaluppi, Marco, Comi, Giancarlo, Greter, Melanie, and Martino, Gianvito
- Subjects
Monocytes -- Research ,Dendritic cells -- Research ,Central nervous system -- Research ,Granulocyte-macrophage colony stimulating factor -- Research ,Multiple sclerosis -- Analysis -- Diagnosis -- Care and treatment ,Health care industry - Abstract
In multiple sclerosis, the pathological interaction between autoreactive Th cells and mononuclear phagocytes in the CNS drives initiation and maintenance of chronic neuroinflammation. Here, we found that intrathecal transplantation of neural stem/precursor cells (NPCs) in mice with experimental autoimmune encephalomyelitis (EAE) impairs the accumulation of inflammatory monocyte-derived cells (MCs) in the CNS, leading to improved clinical outcome. Secretion of IL-23, IL-1, and TNF-[alpha], the cytokines required for terminal differentiation of Th cells, decreased in the CNS of NPC-treated mice, consequently inhibiting the induction of GM-CSF-producing pathogenic Th cells. In vivo and in vitro transcriptome analyses showed that NPC-secreted factors inhibit MC differentiation and activation, favoring the switch toward an antiinflammatory phenotype. Tgfb2 /- NPCs transplanted into EAE mice were ineffective in impairing MC accumulation within the CNS and failed to drive clinical improvement. Moreover, intrathecal delivery of TGF-[beta]2 during the effector phase of EAE ameliorated disease severity. Taken together, these observations identify TGF-[beta]2 as the crucial mediator of NPC immunomodulation. This study provides evidence that intrathecally transplanted NPCs interfere with the CNS-restricted inflammation of EAE by reprogramming infiltrating MCs into antiinflammatory myeloid cells via secretion of TGF- [beta]2., Introduction Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), representing the most common CNS inflammatory disorder and the second leading cause of disability in young [...]
- Published
- 2017
- Full Text
- View/download PDF
5. Neural precursor cell–secreted TGF-β2 redirects inflammatory monocyte-derived cells in CNS autoimmunity
- Author
-
De Feo, Donatella, Merlini, Arianna, Brambilla, Elena, Ottoboni, Linda, Laterza, Cecilia, Menon, Ramesh, Srinivasan, Sundararajan, Farina, Cinthia, Garcia Manteiga, Jose Manuel, Butti, Erica, Bacigaluppi, Marco, Comi, Giancarlo, Greter, Melanie, and Martino, Gianvito
- Published
- 2017
- Full Text
- View/download PDF
6. Endogenous neural stem cells characterization using omics approaches: Current knowledge in health and disease.
- Author
-
Murtaj, Valentina, Butti, Erica, Martino, Gianvito, and Panina-Bordignon, Paola
- Subjects
NEURAL stem cells ,HEALTH literacy ,PLURIPOTENT stem cells ,REGENERATIVE medicine ,METABOLOMICS - Abstract
Neural stem cells (NSCs), an invaluable source of neuronal and glial progeny, have been widely interrogated in the last twenty years, mainly to understand their therapeutic potential. Most of the studies were performed with cells derived from pluripotent stem cells of either rodents or humans, and have mainly focused on their potential in regenerative medicine. High-throughput omics technologies, such as transcriptomics, epigenetics, proteomics, and metabolomics, which exploded in the past decade, represent a powerful tool to investigate the molecular mechanisms characterizing the heterogeneity of endogenous NSCs. The transition from bulk studies to single cell approaches brought significant insights by revealing complex system phenotypes, from the molecular to the organism level. Here, we will discuss the current literature that has been greatly enriched in the "omics era", successfully exploring the nature and function of endogenous NSCs and the process of neurogenesis. Overall, the information obtained from omics studies of endogenous NSCs provides a sharper picture of NSCs function during neurodevelopment in healthy and in perturbed environments. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Persistent modification of forebrain networks and metabolism in rats following adolescent exposure to a 5-HT7 receptor agonist
- Author
-
Canese, Rossella, Zoratto, Francesca, Altabella, Luisa, Porcari, Paola, Mercurio, Laura, de Pasquale, Francesco, Butti, Erica, Martino, Gianvito, Lacivita, Enza, Leopoldo, Marcello, Laviola, Giovanni, and Adriani, Walter
- Published
- 2015
- Full Text
- View/download PDF
8. Neurogenesis or non-neurogenesis: that is the question
- Author
-
Martino, Gianvito, Butti, Erica, and Bacigaluppi, Marco
- Published
- 2014
- Full Text
- View/download PDF
9. Subventricular zone neural progenitors protect striatal neurons from glutamatergic excitotoxicity
- Author
-
Butti, Erica, Bacigaluppi, Marco, Rossi, Silvia, Cambiaghi, Marco, Bari, Monica, Cebrian Silla, Arantxa, Brambilla, Elena, Musella, Alessandra, De Ceglia, Roberta, Teneud, Luis, De Chiara, Valentina, D’Adamo, Patrizia, Garcia-Verdugo, Jose Manuel, Comi, Giancarlo, Muzio, Luca, Quattrini, Angelo, Leocani, Letizia, Maccarrone, Mauro, Centonze, Diego, and Martino, Gianvito
- Published
- 2012
- Full Text
- View/download PDF
10. A nitric oxide releasing derivative of flurbiprofen inhibits experimental autoimmune encephalomyelitis
- Author
-
Furlan, Roberto, Kurne, AslI, Bergami, Alessandra, Brambilla, Elena, Maucci, Raffaella, Gasparini, Laura, Butti, Erica, Comi, Giancarlo, Ongini, Ennio, and Martino, Gianvito
- Published
- 2004
- Full Text
- View/download PDF
11. Neural Stem Cells of the Sub ventricular Zone Contribute to Neuroprotection of the Corpus Callosum after Cuprizone-Induced Demyelination.
- Author
-
Butti, Erica, Bacigaluppi, Marco, Chaabane, Linda, Ruffini, Francesca, Brambilla, Elena, Berera, Giulia, Montonati, Carolina, Quattrini, Angelo, and Martino, Gianvito
- Subjects
- *
NEURAL stem cells , *CORPUS callosum , *DEMYELINATION , *OLIGODENDROGLIA , *MULTIPLE sclerosis - Abstract
Myelin loss occurring in demyelinating diseases, including multiple sclerosis, is the leading cause of long-lasting neurological disability in adults. While endogenous remyelination, driven by resident oligodendrocyte precursor cells (OPCs), might partially compensate myelin loss in the early phases of demyelinating disorders, this spontaneous reparative potential fails at later stages. To investigate the cellular mechanisms sustaining endogenous remyelination in demyelinating disorders, we focused our attention on endogenous neural precursor cells (eNPCs) located within the subventricular zone (SVZ) since this latter area is considered one of the primary sources of new OPCs in the adult forebrain. First, we fate mapped SVZ-eNPCs in cuprizone-induced demyelination and found that SVZ endogenous neural stem/precursor cells are recruited during the remyelination phase to the corpus callosum (CC) and are capable of forming new oligodendrocytes. When we ablated SVZ-derived eNPCs during cuprizone-induced demyelination in female mice, the animals displayed reduced numbers of oligodendrocytes within the lesioned CC. Although this reduction in oligodendrocytes did not impact the ensuing remyelination, eNPC-ablated mice experienced increased axonal loss. Our results indicate that, in toxic models of demyelination, SVZ-derived eNPCs contribute to support axonal survival. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
12. Neural Stem Cell Transplantation Induces Stroke Recovery by Upregulating Glutamate Transporter GLT-1 in Astrocytes.
- Author
-
Bacigaluppi, Marco, Russo, Gianluca Luigi, Peruzzotti-Jametti, Luca, Rossi, Silvia, Sandrone, Stefano, Butti, Erica, De Ceglia, Roberta, Bergamaschi, Andrea, Motta, Caterina, Gallizioli, Mattia, Studer, Valeria, Colombo, Emanuela, Farina, Cinthia, Comi, Giancarlo, Salvatore Politi, Letterio, Muzio, Luca, Villani, Claudia, Invernizzi, Roberto William, Hermann, Dirk Matthias, and Centonze, Diego
- Subjects
NEURAL stem cell transplantation ,STROKE treatment ,GLUTAMATE transporters ,ASTROCYTES ,NEUROPHYSIOLOGY - Abstract
Ischemic stroke is the leading cause of disability, but effective therapies are currently widely lacking. Recovery from stroke is very much dependent on the possibility to develop treatments able to both halt the neurodegenerative process as well as to foster adaptive tissue plasticity. Here we show that ischemic mice treated with neural precursor cell (NPC) transplantation had on neurophysiological analysis, early after treatment, reduced presynaptic release of glutamate within the ipsilesional corticospinal tract (CST), and an enhancedNMDAmediated excitatory transmission in the contralesional CST. Concurrently, NPC-treated mice displayed a reduced CST degeneration, increased axonal rewiring, and augmented dendritic arborization, resulting in long-term functional amelioration persisting up to 60 d after ischemia. The enhanced functional and structural plasticity relied on the capacity of transplanted NPCs to localize in the periischemic and ischemic area, to promote the upregulation of the glial glutamate transporter 1 (GLT-1) on astrocytes and to reduce peri-ischemic extracellular glutamate. The upregulation of GLT-1 induced by transplanted NPCs was found to rely on the secretion of VEGF by NPCs. Blocking VEGF during the first week after stroke reduced GLT-1 upregulation as well as long-term behavioral recovery in NPC-treated mice. Our results show that NPC transplantation, by modulating the excitatory-inhibitory balance and stroke microenvironment, is a promising therapy to ameliorate disability, to promote tissue recovery and plasticity processes after stroke. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
13. Subventricular zone neural progenitors reverse TNF-alpha effects in cortical neurons.
- Author
-
Morini, Raffaella, Ghirardini, Elsa, Butti, Erica, Verderio, Claudia, Martino, Gianvito, and Matteoli, Michela
- Subjects
CEREBRAL cortex ,BRAIN physiology ,TUMOR necrosis factors ,CEREBRAL ventricles ,PROGENITOR cells ,NEURAL transmission ,NEUROPLASTICITY ,ALZHEIMER'S disease ,CENTRAL nervous system physiology - Abstract
Introduction: Tumor necrosis factor alpha (TNFα) plays a physiological role in controlling synaptic transmission and plasticity in the healthy central nervous system by modulating glutamate receptor trafficking to the plasma membrane. TNFα expression is also rapidly induced in response to tissue injury and infection. By promoting the insertion of Ca
2+ permeable-AMPA receptors into the neuronal plasma membrane, this cytokine may cause excessive Ca2+ influx into neurons, thus enhancing neuronal death. Methods: Primary cultures of cortical neurons were obtained from E18 foetal mice and incubated for 24 h with adult neural stem cells (aNPCs) either stimulated with lipopolysaccharide (LPS+aNPCs) or not (aNPCs). Cultures were treated with TNFα (100 ng/ml), and electrophysiological recordings were performed in different conditions to evaluate the effect of the cytokine on neuronal transmission. Results: In this study, we demonstrate that aNPCs from the subventricular zone reverse the effects induced by the cytokine. Moreover, we show that the effect of aNPCs on cortical neurons is mediated by cannabinoid CB1 receptor activation. Conclusion: These data suggest that the role of aNPCs in preventing excitatory neurotransmission potentiation induced by TNFα on cortical neurons may have important implications for pathologies characterized by an inflammatory component affecting cortical neurons such as Alzheimer's disease. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
14. Subventricular zone progenitors in time and space: generating neuronal diversity.
- Author
-
Bernardino, Liliana, Vicario-Abejón, Carlos, and Butti, Erica
- Subjects
NEURONS ,OLFACTORY bulb ,PROGENITOR cells ,BRAIN physiology ,INTERNEURONS - Abstract
The adult mammalian brain harbors a population of cells around their lateral ventricles capable of giving rise to new neurons throughout life. The so-called subventricular zone (SVZ) is a heterogeneous germinative niche in regard to the neuronal types it generates. SVZ progenitors give rise to different olfactory bulb (OB) interneuron types in accordance to their position along the ventricles. Here, I review data showing the difference between progenitors located along different parts of the SVZ axes and ages. I also discuss possible mechanisms for the origin of this diversity. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
15. Role of endogenous neural precursor cells in demyelination and remyelination after cuprizone-induced injury
- Author
-
Butti, Erica, Berera, Giulia, Ruffini, Francesca, Chaabane, Linda, Dina, Giorgia, Quattrini, Angelo, Comi, Giancarlo, and Martino, Gianvito
- Published
- 2014
- Full Text
- View/download PDF
16. Neural stem cell transplantation promotes post-ischemic neuronal plasticity by regulating the expression of glutamate transporters
- Author
-
Bacigaluppi, Marco, Russo, Gianluca Luigi, Peruzzotti-jametti, Luca, Rossi, Silvia, Butti, Erica, De Ceglia, Roberta, Motta, Caterina, Muzio, Luca, Comi, Giancarlo, Centonze, Diego, Invernizzi, Roberto William, Hermann, Dirk Matthias, and Martino, Gianvito
- Published
- 2014
- Full Text
- View/download PDF
17. Gene Therapy Approaches for Autoimmune Diseases of the Central Nervous System and Other Tissues.
- Author
-
Prud’homme, Gérald J., Furlan, Roberto, Butti, Erica, Pluchino, Stefano, and Martino, Gianvito
- Abstract
The gene therapy of autoimmunity has held many promises for the last ten years, owing to its potential as an alternative therapeutic approach for diseases lacking a definitive cure and with a devastating social impact. However, there are still several issues to solve before these approaches would be transferable to humans. Some studies are conceptually non applicable to human diseases. For instance, T and B cell-based antigen-specific approaches are difficult to translate into the clinical practice since the pathogenic (auto)antigens in MS, RA, and IDDM are not yet completely identified and antigen heterogeneity occurs in patients during the course of the disease. From a technological point of view, many gene transfer tools cannot be used in humans due to their (i) toxicity or immunogenicity (i.e., Vaccinia virus, HSV-1, first generation adenoviral vectors), (ii) scarce gene transfer efficiency (i.e., naked DNA, liposomes), and (iii) short-term expression (Vaccinia, HSV-1, naked DNA, liposomes). However, the huge amounts of data generated in the last decade in experimental models have been very instrumental to weight the potential detrimental vs. protective effect of this novel therapeutic approach. We know for example that it is much more safer and efficacious to transfer the “therapeutic” gene directly into the autoimmune target organ rather than into the systemic circulation. This approach has several advantages: (i) restricted area (i.e., the CSF and the synovia) to target thus more efficient gene transfer, (ii) higher levels of transgene expression in the damaged/target area; and, (iii) no peripheral side/toxic effects. In conclusion, while gene therapy approaches of autoimmune diseases are promising, there is a long way ahead before envisaging a wide application of this new technology in human diseases. While gene therapy approaches aimed to recovery loss of functions have shown in experimental models of autoimmunity great efficacy and reproducibility, without over toxic effect, there is still a lot to do for gene therapy protocols aimed to replace non-functioning organs. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
18. Neurogenic and non-neurogenic functions of endogenous neural stem cells.
- Author
-
Butti, Erica, Cusimano, Melania, Bacigaluppi, Marco, and Martino, Gianvito
- Abstract
Adult neurogenesis is a lifelong process that occurs in two main neurogenic niches of the brain, namely in the subventricular zone (SVZ) of the lateral ventricles and in the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus. In the 1960s, studies on adult neurogenesis have been hampered by the lack of established phenotypic markers. The precise tracing of neural stem/progenitor cells (NPCs) was therefore, not properly feasible. After the (partial) identification of those markers, it was the lack of specific tools that hindered a proper experimental elimination and tracing of those cells to demonstrate their terminal fate and commitment. Nowadays, irradiation, cytotoxic drugs as well as genetic tracing/ablation procedures have moved the field forward and increased our understanding of neurogenesis processes in both physiological and pathological conditions. Newly formed NPC progeny from the SVZ can replace granule cells in the olfactory bulbs of rodents, thus contributing to orchestrate sophisticated odor behavior. SGZ-derived new granule cells, instead, integrate within the DG where they play an essential role in memory functions. Furthermore, converging evidence claim that endogenous NPCs not only exert neurogenic functions, but might also have non-neurogenic homeostatic functions by the release of different types of neuroprotective molecules. Remarkably, these non-neurogenic homeostatic functions seem to be necessary, both in healthy and diseased conditions, for example for preventing or limiting tissue damage. In this review, we will discuss the neurogenic and the non-neurogenic functions of adult NPCs both in physiological and pathological conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
19. In Vivo Fate Analysis Reveals the Multipotent and Self-Renewal Features of Embryonic AspM Expressing Cells.
- Author
-
Marinaro, Cinzia, Butti, Erica, Bergamaschi, Andrea, Papale, Alessandro, Furlan, Roberto, Comi, Giancarlo, Martino, Gianvito, and Muzio, Luca
- Subjects
- *
NEUROGLIA , *BRAIN , *TRANSGENIC mice , *CEREBRAL cortex , *DEVELOPMENTAL neurobiology , *NEURAL stem cells , *PROMOTERS (Genetics) , *PROSENCEPHALON - Abstract
Radial Glia (RG) cells constitute the major population of neural progenitors of the mouse developing brain. These cells are located in the ventricular zone (VZ) of the cerebral cortex and during neurogenesis they support the generation of cortical neurons. Later on, during brain maturation, RG cells give raise to glial cells and supply the adult mouse brain of Neural Stem Cells (NSC). Here we used a novel transgenic mouse line expressing the CreERT2 under the control of AspM promoter to monitor the progeny of an early cohort of RG cells during neurogenesis and in the post natal brain. Long term fate mapping experiments demonstrated that AspM-expressing RG cells are multi-potent, as they can generate neurons, astrocytes and oligodendrocytes of the adult mouse brain. Furthermore, AspM descendants give also rise to proliferating progenitors in germinal niches of both developing and post natal brains. In the latter -i.e. the Sub Ventricular Zone- AspM descendants acquired several feature of neural stem cells, including the capability to generate neurospheres in vitro. We also performed the selective killing of these early progenitors by using a Nestin-GFPflox-TK allele. The forebrain specific loss of early AspM expressing cells caused the elimination of most of the proliferating cells of brain, a severe derangement of the ventricular zone architecture, and the impairment of the cortical lamination. We further demonstrated that AspM is expressed by proliferating cells of the adult mouse SVZ that can generate neuroblasts fated to become olfactory bulb neurons. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
20. Inflammation Triggers Synaptic Alteration and Degeneration in Experimental Autoimmune Encephalomyelitis.
- Author
-
Centonze, Diego, Muzio, Luca, Rossi, Silvia, Cavasinni, Francesca, De Chiara, Valentina, Bergami, Alessandra, Musella, Alessandra, D'Amelio, Marcello, Cavallucci, Virve, Martorana, Alessandro, Bergamaschi, Andrea, Cencioni, Maria Teresa, Diamantini, Adamo, Butti, Erica, Comi, Giancarlo, Bernardi, Giorgio, Cecconi, Francesco, Battistini, Luca, Furlan, Roberto, and Martino, Gianvito
- Subjects
CENTRAL nervous system diseases ,ENCEPHALOMYELITIS ,TUMOR necrosis factors ,CYTOKINES ,VIRUS diseases - Abstract
Neurodegeneration is the irremediable pathological event occurring during chronic inflammatory diseases of the CNS. Here we show that, in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, inflammation is capable in enhancing glutamate transmission in the striatum and in promoting synaptic degeneration and dendritic spine loss. These alterations occur early in the disease course, are independent of demyelination, and are strongly associated with massive release of tumor necrosis factor-α from activated microglia. CNS invasion by myelin-specific blood-borne immune cells is the triggering event, and the downregulation of the early gene Arc/Arg3.1, leading to the abnormal expression and phosphorylation of AMPA-receptors, represents a culminating step in this cascade of neurodegenerative events. Accordingly, EAE-induced synaptopathy subsided during pharmacological blockade of AMPA receptors. Our data establish a link between neuroinflammation and synaptic degeneration and calls for early neuroprotective therapies in chronic inflammatory diseases of the CNS. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
21. Endogenous neural precursor cells in health and disease.
- Author
-
Bacigaluppi, Marco, Sferruzza, Giacomo, Butti, Erica, Ottoboni, Linda, and Martino, Gianvito
- Subjects
- *
DENTATE gyrus , *PROGENITOR cells , *OLFACTORY bulb , *AGE , *NEURAL stem cells - Abstract
• Neural precursor cells accomplish important functions for brain tissue homeostasis. • Neural precursor cells provide new cells for the olfactory bulb and hippocampus (neurogenic role). • Neural precursor cells regulate brain functions through the release of soluble factors (non-neurogenic role). • In pathological conditions, neural precursor cells contribute to restraining tissue damage. • Neurodegenerative diseases and physiological aging are accompanied by neural precursor cell dysfunctions. Neurogenesis persists in the adult brain of mammals in the subventricular zone (SVZ) of the lateral ventricles and in the subgranular zone (SGZ) of the dentate gyrus (DG). The complex interactions between intrinsic and extrinsic signals provided by cells in the niche but also from distant sources regulate the fate of neural stem/progenitor cells (NPCs) in these sites. This fine regulation is perturbed in aging and in pathological conditions leading to a different NPC behavior, tailored to the specific physio-pathological features. Indeed, NPCs exert in physiological and pathological conditions important neurogenic and non-neurogenic regulatory functions and participate in maintaining and protecting brain tissue homeostasis. In this review, we discuss intrinsic and extrinsic signals that regulate NPC activation and NPC functional role in various homeostatic and non-homeostatic conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
22. Neural precursor cell-secreted TGF-β2 redirects inflammatory monocyte-derived cells in CNS autoimmunity
- Author
-
Gianvito Martino, Jose Manuel Garcia Manteiga, Melanie Greter, Giancarlo Comi, Sundararajan Srinivasan, Arianna Merlini, Cinthia Farina, Marco Bacigaluppi, Cecilia Laterza, Donatella De Feo, Elena Brambilla, Ramesh Menon, Linda Ottoboni, Erica Butti, University of Zurich, Martino, Gianvito, Feo, Donatella De, Merlini, Arianna, Brambilla, Elena, Ottoboni, Linda, Laterza, Cecilia, Menon, Ramesh, Srinivasan, Sundararajan, Farina, Cinthia, Manteiga, Jose Manuel Garcia, Butti, Erica, Bacigaluppi, Marco, Comi, Giancarlo, and Greter, Melanie
- Subjects
0301 basic medicine ,Multiple Sclerosis ,Mice, 129 Strain ,Cellular differentiation ,Inflammation ,610 Medicine & health ,2700 General Medicine ,Dendritic Cell ,Monocyte ,10263 Institute of Experimental Immunology ,Monocytes ,Transcriptome ,Immunomodulation ,03 medical and health sciences ,Transforming Growth Factor beta2 ,0302 clinical medicine ,Neural Stem Cells ,Precursor cell ,Multiple Sclerosi ,Animals ,Medicine ,Neural Stem Cell ,Cytokine ,Neuroinflammation ,Cells, Cultured ,business.industry ,Animal ,Medicine (all) ,Experimental autoimmune encephalomyelitis ,Brain ,Cell Differentiation ,Dendritic Cells ,General Medicine ,T-Lymphocytes, Helper-Inducer ,medicine.disease ,Transplantation ,Mice, Inbred C57BL ,030104 developmental biology ,Cancer research ,Cytokines ,570 Life sciences ,biology ,Female ,Microglia ,medicine.symptom ,business ,Reprogramming ,030217 neurology & neurosurgery ,Research Article - Abstract
In multiple sclerosis, the pathological interaction between autoreactive Th cells and mononuclear phagocytes in the CNS drives initiation and maintenance of chronic neuroinflammation. Here, we found that intrathecal transplantation of neural stem/precursor cells (NPCs) in mice with experimental autoimmune encephalomyelitis (EAE) impairs the accumulation of inflammatory monocyte-derived cells (MCs) in the CNS, leading to improved clinical outcome. Secretion of IL-23, IL-1, and TNF-α, the cytokines required for terminal differentiation of Th cells, decreased in the CNS of NPC-treated mice, consequently inhibiting the induction of GM-CSF-producing pathogenic Th cells. In vivo and in vitro transcriptome analyses showed that NPC-secreted factors inhibit MC differentiation and activation, favoring the switch toward an antiinflammatory phenotype. Tgfb2-/-NPCs transplanted into EAE mice were ineffective in impairing MC accumulation within the CNS and failed to drive clinical improvement. Moreover, intrathecal delivery of TGF-β2 during the effector phase of EAE ameliorated disease severity. Taken together, these observations identify TGF-β2 as the crucial mediator of NPC immunomodulation. This study provides evidence that intrathecally transplanted NPCs interfere with the CNS-restricted inflammation of EAE by reprogramming infiltrating MCs into antiinflammatory myeloid cells via secretion of TGF-β2.
- Published
- 2017
23. Neural Stem Cell Transplantation Induces Stroke Recovery by Upregulating Glutamate Transporter GLT-1 in Astrocytes
- Author
-
Valeria Studer, Stefano Sandrone, Luca Peruzzotti-Jametti, Luca Muzio, Silvia Rossi, Claudia Villani, Dirk M. Hermann, Andrea Bergamaschi, Caterina Motta, Erica Butti, Marco Bacigaluppi, Roberto W. Invernizzi, Cinthia Farina, Letterio S. Politi, Roberta De Ceglia, Gianluca Russo, Giancarlo Comi, Gianvito Martino, Mattia Gallizioli, Diego Centonze, Emanuela Colombo, Bacigaluppi, Marco, Russo, Gianluca Luigi, Peruzzotti-Jametti, Luca, Rossi, Silvia, Sandrone, Stefano, Butti, Erica, de Ceglia, Roberta, Bergamaschi, Andrea, Motta, Caterina, Gallizioli, Mattia, Studer, Valeria, Colombo, Emanuela, Farina, Cinthia, Comi, Giancarlo, Politi, Letterio Salvatore, Muzio, Luca, Villani, Claudia, Invernizzi, Roberto William, Hermann, Dirk Matthia, Centonze, Diego, and Martino, Gianvito
- Subjects
0301 basic medicine ,Male ,Vascular Endothelial Growth Factor A ,Patch-Clamp Techniques ,medicine.medical_treatment ,Patch-Clamp Technique ,ischemia ,neurophysiology ,plasticity ,recovery ,stem cell ,transplantation ,Medizin ,Brain Ischemia ,Brain ischemia ,Mice ,0302 clinical medicine ,Neural Stem Cells ,Ischemia ,Recovery ,Neural Stem Cell ,Stroke ,Stem cell ,Neuronal Plasticity ,Behavior, Animal ,General Neuroscience ,Glutamate receptor ,Articles ,Cerebral Infarction ,Neural stem cell ,Up-Regulation ,Excitatory Amino Acid Transporter 2 ,Settore MED/26 - Neurologia ,Stroke recovery ,Astrocyte ,Plasticity ,Neurophysiology ,Glutamic Acid ,Biology ,03 medical and health sciences ,Precursor cell ,medicine ,Animals ,Transplantation ,Neuroscience (all) ,Animal ,Recovery of Function ,medicine.disease ,Mice, Inbred C57BL ,stomatognathic diseases ,030104 developmental biology ,Astrocytes ,Neuroscience ,030217 neurology & neurosurgery ,Stem Cell Transplantation - Abstract
Ischemic stroke is the leading cause of disability, but effective therapies are currently widely lacking. Recovery from stroke is very much dependent on the possibility to develop treatments able to both halt the neurodegenerative process as well as to foster adaptive tissue plasticity. Here we show that ischemic mice treated with neural precursor cell (NPC) transplantation had on neurophysiological analysis, early after treatment, reduced presynaptic release of glutamate within the ipsilesional corticospinal tract (CST), and an enhanced NMDA-mediated excitatory transmission in the contralesional CST. Concurrently, NPC-treated mice displayed a reduced CST degeneration, increased axonal rewiring, and augmented dendritic arborization, resulting in long-term functional amelioration persisting up to 60 d after ischemia. The enhanced functional and structural plasticity relied on the capacity of transplanted NPCs to localize in the peri-ischemic and ischemic area, to promote the upregulation of the glial glutamate transporter 1 (GLT-1) on astrocytes and to reduce peri-ischemic extracellular glutamate. The upregulation of GLT-1 induced by transplanted NPCs was found to rely on the secretion of VEGF by NPCs. Blocking VEGF during the first week after stroke reduced GLT-1 upregulation as well as long-term behavioral recovery in NPC-treated mice. Our results show that NPC transplantation, by modulating the excitatory–inhibitory balance and stroke microenvironment, is a promising therapy to ameliorate disability, to promote tissue recovery and plasticity processes after stroke.SIGNIFICANCE STATEMENTTissue damage and loss of function occurring after stroke can be constrained by fostering plasticity processes of the brain. Over the past years, stem cell transplantation for repair of the CNS has received increasing interest, although underlying mechanism remain elusive. We here show that neural stem/precursor cell transplantation after ischemic stroke is able to foster axonal rewiring and dendritic plasticity and to induce long-term functional recovery. The observed therapeutic effect of neural precursor cells seems to underlie their capacity to upregulate the glial glutamate transporter on astrocytes through the vascular endothelial growth factor inducing favorable changes in the electrical and molecular stroke microenvironment. Cell-based approaches able to influence plasticity seem particularly suited to favor poststroke recovery.
- Published
- 2016
24. Gene therapy for autoimmune diseases.
- Author
-
Furlan R, Butti E, Pluchino S, and Martino G
- Subjects
- Arthritis, Rheumatoid genetics, Arthritis, Rheumatoid therapy, Autoimmune Diseases immunology, Autoimmune Diseases pathology, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 therapy, Genetic Therapy instrumentation, Humans, Multiple Sclerosis genetics, Multiple Sclerosis therapy, Autoimmune Diseases genetics, Autoimmune Diseases therapy, Genetic Therapy methods
- Abstract
Autoimmune diseases are threatening an increasing number of patients in developed countries, representing one of the major causes of disability and an enormous social cost. Current therapies mainly treat the symptoms of autoimmune diseases and are only partially able to interfere with disease evolution, and therefore decrease the degree of physical impairment. Thus, the development of new therapeutic strategies is imperative. This review focuses on gene therapy, as one possible alternative approach to the treatment of autoimmune disorders. The potential of gene therapy to specifically target tissues affected by autoimmune aggression, and its ability to interfere with the destructive pathogenic process while providing functional replacement and fostering reparative mechanisms will be emphasized. Gene therapy studies in experimental models of diabetes, rheumatoid arthritis and multiple sclerosis are reviewed.
- Published
- 2004
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.