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

• Published in: The Journal of clinical investigation 2015-09, Vol.125 (9), p.3642-3656
• Main Authors: Mozafari, Sabah, Laterza, Cecilia, Roussel, Delphine, Bachelin, Corinne, Marteyn, Antoine, Deboux, Cyrille, Martino, Gianvito, Baron-Van Evercooren, Anne
• Format: Article
• Language: English
• Subjects: Animals; Biomedical research; Cell Differentiation; Demyelinating Diseases - metabolism; Demyelinating Diseases - pathology; Demyelinating Diseases - therapy; Experiments; Gene expression; Induced Pluripotent Stem Cells - metabolism; Induced Pluripotent Stem Cells - pathology; Mice; Mice, Knockout; Multiple sclerosis; Myelin Sheath - metabolism; Myelination; Neural Stem Cells - metabolism; Neural Stem Cells - pathology; Neural Stem Cells - transplantation; Regenerative Medicine - methods; Skin - metabolism; Skin - pathology; Software; Stem Cell Transplantation; Stem cells; Studies
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci80437

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.