Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 125, Issue 9, Pages 3642-3656Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI80437
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Funding
- INSERM
- European Leukodystrophy Foundation (ELA) [ELA 2010-003C5]
- US National Multiple Sclerosis Society (NMSS) [RG4733A3/1]
- Target-Brain EU-FP7 project [HEALTH-F2-2012-279017]
- NEUROKINE EU-FP7 ITN project
- program Investissements d'Avenir [ANR-10-IAIHU-06, ANR-11-INBS-0011-NeurATRIS]
- Multiple Sclerosis International Federation
- Ecole de Neurosciences de Paris (ENP)
- Region Ile de France (DIM Cerveau et Pensee)
- EDF Foundation
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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.
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