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

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

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.

Authors

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

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Figure 9

miPS-derived myelin improves conduction of the dysfunctional Shi/Shi Rag2–/– axons.

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miPS-derived myelin improves conduction of the dysfunctional Shi/Shi Rag...
(A) N1 latency was measured following SSEP in different groups of Shi/Shi Rag2–/– mice 6 wpg or medium injection. miPS-derived myelin significantly decreased conduction latency in intact (P = 0.01) or demyelinated spinal cord injected with medium (P = 0.02). (B) Evaluation of axonal conduction velocity in the different groups. While no difference was detected in demyelinated and medium-treated mice over intact mice, grafted animals showed a significant increase in conduction velocities over intact (P = 0.03) or demyelinated and medium-treated mice (P = 0.02). (C–F) Representative SSEP profiles for intact (C), and lesioned mice injected with medium (D), miPS-NPCs (E), mE-NPCs (F), and grafted mice (n = 4–6 mice per group). Mann Whitney test was used for the statistical analysis. S, Stimulation. *P < 0.05. Scales in profiles: 5 ms (horizontal) or 2 μV (vertical) per divisions.