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, Gianvito Martino

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish
Article number2597
JournalNature Communications
Volume4
DOIs
Publication statusPublished - Oct 29 2013

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Induced Pluripotent Stem Cells
secretions
Neural Stem Cells
stem cells
Demyelinating Diseases
Stem cells
laser induced fluorescence
Oligodendroglia
Neurology
Myelin Sheath
myelin
Tissue Preservation
Leukemia Inhibitory Factor
central nervous system
Autoimmune Experimental Encephalomyelitis
Central Nervous System Diseases
Cell Transplantation
Neuroprotective Agents
Blood-Brain Barrier
Infiltration

ASJC Scopus subject areas

  • Chemistry(all)
  • Physics and Astronomy(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ipsc-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF. / Laterza, Cecilia; Merlini, Arianna; De Feo, Donatella; Ruffini, Francesca; Menon, Ramesh; Onorati, Marco; Fredrickx, Evelien; Muzio, Luca; Lombardo, Angelo; Comi, Giancarlo; Quattrini, Angelo; Taveggia, Carla; Farina, Cinthia; Cattaneo, Elena; Martino, Gianvito.

In: Nature Communications, Vol. 4, 2597, 29.10.2013.

Research output: Contribution to journalArticle

Laterza, Cecilia ; Merlini, Arianna ; De Feo, Donatella ; Ruffini, Francesca ; Menon, Ramesh ; Onorati, Marco ; Fredrickx, Evelien ; Muzio, Luca ; Lombardo, Angelo ; Comi, Giancarlo ; Quattrini, Angelo ; Taveggia, Carla ; Farina, Cinthia ; Cattaneo, Elena ; Martino, Gianvito. / Ipsc-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF. In: Nature Communications. 2013 ; Vol. 4.
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