title: Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism.
abstract: In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection.
authors: Neuroimmunology Unit-DIBIT, Vita-Salute University, San Raffaele Hospital, via Olgettina 58, 20132 Milan, Italy.
authors: Stefano
authors: S
authors: Pluchino
authors: Lucia
authors: L
authors: Zanotti
authors: Barbara
authors: B
authors: Rossi
authors: Elena
authors: E
authors: Brambilla
authors: Linda
authors: L
authors: Ottoboni
authors: Giuliana
authors: G
authors: Salani
authors: Marianna
authors: M
authors: Martinello
authors: Alessandro
authors: A
authors: Cattalini
authors: Alessandra
authors: A
authors: Bergami
authors: Roberto
authors: R
authors: Furlan
authors: Giancarlo
authors: G
authors: Comi
authors: Gabriela
authors: G
authors: Constantin
authors: Gianvito
authors: G
authors: Martino
mesh_terms: D000818:Animals; D017209:Apoptosis; D016380:Brain Tissue Transplantation; D002448:Cell Adhesion; D002454:Cell Differentiation; D002490:Central Nervous System / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D002633:Chemotaxis; D002908:Chronic Disease; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D039041:Integrin alpha4beta1 / Q000378:metabolism; D051379:Mice; D008863:Microspheres; D039902:Multipotent Stem Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology / Q000637:transplantation*; D018696:Neuroprotective Agents / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D039041:Integrin alpha4beta1; D018696:Neuroprotective Agents; D019707:Receptors, Chemokine