TY - JOUR
T1 - Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism
AU - Pluchino, Stefano
AU - Zanotti, Lucia
AU - Rossi, Barbara
AU - Brambilla, Elena
AU - Ottoboni, Linda
AU - Salani, Giuliana
AU - Martinello, Marianna
AU - Cattalini, Alessandro
AU - Bergami, Alessandra
AU - Furlan, Roberto
AU - Comi, Giancarlo
AU - Constantin, Gabriela
AU - Martino, Gianvito
PY - 2005/7/14
Y1 - 2005/7/14
N2 - 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.
AB - 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.
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U2 - 10.1038/nature03889
DO - 10.1038/nature03889
M3 - Article
C2 - 16015332
AN - SCOPUS:22444450988
VL - 436
SP - 266
EP - 271
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7048
ER -