Injeção de neuroesferas adultas

Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis

Stefano Pluchino1, Angelo Quattrini2,3, Elena Brambilla1, Angela Gritti4, Giuliana Salani1, Giorgia Dina2, Rossella Galli4, Ubaldo Del Carro3, Stefano Amadio3, Alessandra Bergami1, Roberto Furlan1,3, Giancarlo Comi3, Angelo L. Vescovi4 & Gianvito Martino1,3

Neuroimmunology Unit—DIBIT, San Raffaele Hospital, via Olgettina 58, 20132 Milano, Italy

Neuropathology Unit, San Raffaele Hospital, via Olgettina 58, 20132 Milano, Italy

Stem Cell Research Institute, San Raffaele Hospital, via Olgettina 58, 20132 Milano, Italy

Department of Neurology and Neurophysiology, San Raffaele Hospital, via Olgettina 58, 20132 Milano, Italy

Correspondence to: Angelo L. Vescovi4Gianvito Martino1,3 Correspondence and requests for materials should be addressed to G.M. (e-mail: Email: martino.gianvito@hsr.it) or A.L.V. (e-mail: Email: vescovi@tin.it).

Top of pageAbstract

Widespread demyelination and axonal loss are the pathological hallmarks of multiple sclerosis. The multifocal nature of this chronic inflammatory disease of the central nervous system complicates cellular therapy and puts emphasis on both the donor cell origin and the route of cell transplantation. We established syngenic adult neural stem cell cultures and injected them into an animal model of multiple sclerosis—experimental autoimmune encephalomyelitis (EAE) in the mouse—either intravenously or intracerebroventricularly. In both cases, significant numbers of donor cells entered into demyelinating areas of the central nervous system and differentiated into mature brain cells. Within these areas, oligodendrocyte progenitors markedly increased, with many of them being of donor origin and actively remyelinating axons. Furthermore, a significant reduction of astrogliosis and a marked decrease in the extent of demyelination and axonal loss were observed in transplanted animals. The functional impairment caused by EAE was almost abolished in transplanted mice, both clinically and neurophysiologically. Thus, adult neural precursor cells promote multifocal remyelination and functional recovery after intravenous or intrathecal injection in a chronic model of multiple sclerosis.

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