iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF

Cecilia Laterza, Arianna Merlini, Donatella De Feo, Francesca Ruffini, Ramesh Menon, Marco Onorati, Evelien Fredrickx, Luca Muzio, Angelo Lombardo, Giancarlo Comi, Angelo Quattrini, Carla Taveggia, Cinthia Farina, Elena Cattaneo and Gianvito Martino ()
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Cecilia Laterza: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Arianna Merlini: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Donatella De Feo: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Francesca Ruffini: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Ramesh Menon: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Marco Onorati: Università degli Studi di Milano
Evelien Fredrickx: Axo-Glia Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Luca Muzio: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Angelo Lombardo: San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute
Giancarlo Comi: Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Angelo Quattrini: Neuropathology Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Carla Taveggia: Axo-Glia Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Cinthia Farina: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute
Elena Cattaneo: Università degli Studi di Milano
Gianvito Martino: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute

Nature Communications, 2013, vol. 4, issue 1, 1-16

Abstract: Abstract The possibility of generating neural stem/precursor cells (NPCs) from induced pluripotent stem cells (iPSCs) has opened a new avenue of research that might nurture bench-to-bedside translation of cell transplantation protocols in central nervous system myelin disorders. Here we show that mouse iPSC-derived NPCs (miPSC-NPCs)—when intrathecally transplanted after disease onset—ameliorate clinical and pathological features of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Transplanted miPSC-NPCs exert the neuroprotective effect not through cell replacement, but through the secretion of leukaemia inhibitory factor that promotes survival, differentiation and the remyelination capacity of both endogenous oligodendrocyte precursors and mature oligodendrocytes. The early preservation of tissue integrity limits blood–brain barrier damage and central nervous system infiltration of blood-borne encephalitogenic leukocytes, ultimately responsible for demyelination and axonal damage. While proposing a novel mechanism of action, our results further expand the therapeutic potential of NPCs derived from iPSCs in myelin disorders.

Date: 2013
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DOI: 10.1038/ncomms3597

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