Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice

Sabah Mozafari, Cecilia Laterza, Delphine Roussel, Corinne Bachelin, Antoine Marteyn, Cyrille Deboux, Gianvito Martino, Anne Baron Van Evercooren

Research output: Contribution to journalArticle

Abstract

Induced pluripotent stem cell-derived (iPS-derived) neural precursor cells may represent the ideal autologous cell source for cell-based therapy to promote remyelination and neuroprotection in myelin diseases. So far, the therapeutic potential of reprogrammed cells has been evaluated in neonatal demyelinating models. However, the repair efficacy and safety of these cells has not been well addressed in the demyelinated adult CNS, which has decreased cell plasticity and scarring. Moreover, it is not clear if these induced pluripotent-derived cells have the same reparative capacity as physiologically committed CNS-derived precursors. Here, we performed a side-by-side comparison of CNS-derived and skin-derived neural precursors in culture and following engraftment in murine models of adult spinal cord demyelination. Grafted induced neural precursors exhibited a high capacity for survival, safe integration, migration, and timely differentiation into mature bona fide oligodendrocytes. Moreover, grafted skin-derived neural precursors generated compact myelin around host axons and restored nodes of Ranvier and conduction velocity as efficiently as CNS-derived precursors while outcompeting endogenous cells. Together, these results provide important insights into the biology of reprogrammed cells in adult demyelinating conditions and support use of these cells for regenerative biomedicine of myelin diseases that affect the adult CNS.

Original languageEnglish
Pages (from-to)3642-3656
Number of pages15
JournalJournal of Clinical Investigation
Volume125
Issue number9
DOIs
Publication statusPublished - Sep 1 2015

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Myelin Sheath
Skin
Ranvier's Nodes
Induced Pluripotent Stem Cells
Oligodendroglia
Demyelinating Diseases
Cell- and Tissue-Based Therapy
Cicatrix
Axons
Cell Biology
Spinal Cord
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mozafari, S., Laterza, C., Roussel, D., Bachelin, C., Marteyn, A., Deboux, C., ... Evercooren, A. B. V. (2015). Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice. Journal of Clinical Investigation, 125(9), 3642-3656. https://doi.org/10.1172/JCI80437

Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice. / Mozafari, Sabah; Laterza, Cecilia; Roussel, Delphine; Bachelin, Corinne; Marteyn, Antoine; Deboux, Cyrille; Martino, Gianvito; Evercooren, Anne Baron Van.

In: Journal of Clinical Investigation, Vol. 125, No. 9, 01.09.2015, p. 3642-3656.

Research output: Contribution to journalArticle

Mozafari, S, Laterza, C, Roussel, D, Bachelin, C, Marteyn, A, Deboux, C, Martino, G & Evercooren, ABV 2015, 'Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice', Journal of Clinical Investigation, vol. 125, no. 9, pp. 3642-3656. https://doi.org/10.1172/JCI80437
Mozafari, Sabah ; Laterza, Cecilia ; Roussel, Delphine ; Bachelin, Corinne ; Marteyn, Antoine ; Deboux, Cyrille ; Martino, Gianvito ; Evercooren, Anne Baron Van. / Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice. In: Journal of Clinical Investigation. 2015 ; Vol. 125, No. 9. pp. 3642-3656.
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